International Immunology

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (158) Request Permissions Google Scholar Articles by Takeuchi, O. Articles by Akira, S. Search for Related Content PubMed PubMed Citation Articles by Takeuchi, O. Articles by Akira, S. Social Bookmarking          What's this?

International Immunology, Vol. 12, No. 1, 113-117, January 2000
© 2000 Japanese Society for Immunology

Cellular responses to bacterial cell wall components are mediated through MyD88-dependent signaling cascades

Osamu Takeuchi^1,2, Kiyoshi Takeda^1,2, Katsuaki Hoshino^1,2, Osamu Adachi^1,2, Tomohiko Ogawa³ and Shizuo Akira^1,2

¹ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and
² CREST of Japan Science and Technology Corp., 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
³ Department of Oral Microbiology, Asahi University School of Dentistry, 1851-1 Hozumi, Hozumi-Cho, Motosu-Gun, Gifu 501-0296, Japan

Correspondence to: S. Akira

	Abstract

Top Abstract Introduction References

 
MyD88 is an adaptor molecule essential for signaling via the Toll-like receptor (TLR)/IL-1 receptor family. TLR4 is a member of the TLR family and a point mutation in the Tlr4 gene causes hyporesponsiveness to lipopolysaccharide (LPS) in C3H/HeJ mice. We have previously shown that both TLR4- and MyD88-deficient mice are hyporesponsive to LPS. In this study we examined the responsiveness of these two knockout mice to various bacterial cell wall components. Cells from TLR4-deficient mice responded to several kinds of LPS, peptidoglycan and crude cell wall preparation from Gram-positive bacteria and mycobacterial lysates. In contrast, macrophages and splenocytes from MyD88-deficient mice did not respond to any of the bacterial components we tested. These results show that MyD88 is essential for the cellular response to bacterial cell wall components.

Keywords: Gram-positive bacteria, innate immunity, lipopolysaccharide, macrophage, Toll-like receptor

	Introduction

Top Abstract Introduction References

 
The innate immune system is characterized by the use of germline-encoded receptors for pathogen recognition. Drosophila depend entirely on the innate response for their host defense (1). Regulation of the antifungal immune response in adult flies has been shown to involve the Toll receptor (2), which was originally identified as a receptor essential for dorsoventral patterning during early embryonic development (3). Toll is a type I transmembrane receptor whose extracellular domain contains a leucine-rich repeat and whose cytoplasmic domain is analogous to that of the mammalian IL-1 receptor (IL-1R) family (4). Similar to IL-1 signaling, binding of Toll by the extracellular ligand Spatzle leads to activation of Dorsal, an NFB-like transcription factor (4). In mutants deficient in the Toll pathway, induction of the antifungal peptide drosomycin is dramatically affected (2). Mutation in 18-wheeler, another Toll family member, results in a defect in the antibacterial host defense but does not affect the antifungal response (5). Thus, particular pathogens induce the production of specific antimicrobial peptides in Drosophila through the selective activation of the Toll pathway (6).

Innate immunity in vertebrates plays a similar role in the detection of invading infectious organisms, and subsequently instructs adaptive immune system by producing proinflammatory cytokines such as tumor necrosis factor (TNF)-, IL-1 and IL-6, as well as co-stimulatory molecules on the cell surfaces of immune cells (1). Recently, six human homologues of Drosophila Toll, designated Toll-like receptors (TLR) 1–6, have been reported (7–9). TLR2 has been shown to be a signaling receptor that is activated by lipopolysaccharide (LPS), a part of the outer membrane of Gram-negative bacteria (10,11). Further, it has recently been shown that LPS hyporesponsiveness in the mouse strain C3H/HeJ is due to a missense point mutation in the Tlr4 gene (12–14). Macrophages and B cells from TLR4-deficient mice are hyporesponsive to LPS, indicating that TLR4 is required for LPS signaling (14).

MyD88 is an adaptor molecule essential for IL-1R family signaling (15–17). Triggering of the intracellular IL-1R family signaling cascade requires the recruitment of MyD88 to the receptor complex, which then relays a signal to NFB via IL-1R-associated kinase (IRAK). TLR2 and TLR4 have been reported to also utilize MyD88 as an adaptor molecule in vitro (11,18,19). Other TLR family members that contain cytoplasmic domains homologous to that of IL-1R might also share MyD88. We have recently shown that MyD88-deficient mice are highly resistant to LPS-induced shock, and that both macrophages and B cells from MyD88-deficient mice displayed no biological responses to LPS (20). Recently, it has been shown that overexpression of TLR2 conferred responsiveness to several Gram-positive bacterial components such as peptidoglycan (PGN) (21,22), lipoteichoic acid (LTA) (21) and bacterial lipoproteins (23,24) in vitro. To investigate the roles of MyD88 in the recognition of specific pathogen components, we examined and compared the responsiveness of TLR4- and MyD88-deficient mice to various bacterial cell wall components.

We first examined the responsiveness of mouse cells to LPS derived from Salmonella minnesota Re-595. Peritoneal macrophages from wild-type, TLR4-deficient and MyD88-deficient mice were cultured in the presence of various concentrations of Re-595 LPS, and the production of TNF- was measured. Secretions of TNF- from wild-type macrophages increased in a dose-dependent manner. In contrast, macrophages from TLR4-deficient or MyD88-deficient mice did not produce any detectable amounts of TNF- in response to LPS, even when added to a concentration of 100 µg/ml (Fig. 1A). We next examined the responsiveness of splenocytes to Re-595 LPS. Splenocytes were cultured in the presence of various concentrations of LPS. Whereas this stimulation elicited a dose-dependent mitogenic response in wild-type splenocytes, no LPS-induced proliferative response was observed in splenocytes from either TLR4- or MyD88-deficient mice (Fig. 1B). Thus, the responses of both TLR4- and MyD88-deficient mice to S. minnesota Re-595 LPS are almost completely abrogated.

View larger version (29K): [in this window] [in a new window]   Fig. 1. Responsiveness to S. minnesota Re-595 and P. gingivalis LPS. (A) Mice were i.p. injected with 2 ml of 4% thioglycollate. Three days later, peritoneal exudate cells were isolated. The cells from wild-type, and TLR4- and MyD88-deficient mice were cultured with the indicated amount of S. minnesota Re-595 LPS (Sigma) for 24 h. Concentrations of TNF- in the culture supernatants were measured by ELISA (Genzyme, Cambridge, MA). (B) Splenocytes (1x105) were isolated and cultured with the indicated concentrations of S. minnesota Re-595 LPS for 48 h. Then 1 µCi of [3H]thymidine (DuPont, Boston, MA) was pulsed for the last 8 h. 3H incorporation was measured by a ß scintillation counter (Packard, Meriden, CT). (C) Peritoneal macrophages from wild-type, and TLR4- and MyD88- deficient mice were cultured with the indicated concentrations of P. gingivalis LPS for 24 h. Concentrations of TNF- in the culture supernatants were measured by ELISA. Preparation of P. gingivalis LPS is as described previously (25). (D) Splenocytes were cultured with the indicated concentrations of P. gingivalis LPS for 48 h. Then 1 µCi of [3H]thymidine was pulsed for the last 8 h. 3H incorporation was measured by a scintillation counter.

 
We next examined the response of these mice to LPS prepared from Porphyromonas gingivalis 381, a Gram-negative bacterium and peridontopathic organisms of major importance (25). P. gingivalis LPS displays an interesting property in its ability to activate cells from the otherwise LPS-hyporesponsive C3H/HeJ mice (25). As shown in Fig. 1(C), P. gingivalis LPS induced TNF- in a dose-dependent manner in macrophages from wild-type mice. P. gingivalis LPS also induced TNF- in TLR4-deficient macrophages, similar to C3H/HeJ macrophages, although the level was about one-third that of wild-type macrophages. In contrast, MyD88-deficient macrophages did not produce any detectable TNF-, even when stimulated with high concentrations of LPS. Splenocytes from TLR4-deficient mice exhibited a significant, albeit lower, proliferative response to P. gingivalis LPS. In contrast, proliferation of splenocytes was not observed with MyD88-deficient splenocytes (Fig. 1D). Thus, TLR4-deficient mice were partially defective and MyD88-deficient mice almost completely defective in their response to P. gingivalis LPS. These results indicate that MyD88 is essential for, and that TLR4 contributes in part to, the signaling elicited by P. gingivalis LPS.

To rule out the possibility that the cells from TLR4- and MyD88-deficient mice are inert to all stimuli, we analyzed their responsiveness to other stimuli. Splenocytes from TLR4- and MyD88-deficient mice proliferated normally in response to IL-4 plus anti-IgM antibody or anti-CD40 antibody (Fig. 2A). IFN--induced augmentation of MHC class II expression on peritoneal macrophages was also enhanced to a similar extent in wild-type, and TLR4- and MyD88-deficient mice (Fig. 2B). Peritoneal macrophages from both TLR4- and MyD88-deficient mice phagocytosed latex microspheres normally (Fig. 2C). Thus, the responses of macrophages and splenocytes from either TLR4- or MyD88-deficient mice to these other stimuli were not impaired, indicating that these mutant cells are specifically defective in their response to LPS.

View larger version (42K): [in this window] [in a new window]   Fig. 2. Normal responses to IL-4 and IFN- and normal phagocytic activity in TLR4- and MyD88-deficient mice. (A) Splenocytes were cultured with IL-4 (Genzyme) plus anti-IgM Ab or anti-CD40 Ab (PharMingen, San Diego, CA) for 48 h. Then 1 µCi of [3H]thymidine was pulsed for the last 8 h. 3H incorporation was measured by a scintillation counter. 3H incorporations (c.p.m.) in cells from wild-type, and TLR4- and MyD88-deficient mice without stimulation were 161, 134 and 175 respectively. (B) Mice were injected i.p. with 5000 U of IFN- (Genzyme) or PBS. Three days later, peritoneal macrophages were collected and stained with biotin-conjugated anti-I-Ab antibody (PharMingen) followed by streptavidin–FITC (PharMingen). Stained cells were analyzed on FACSCalibur using CellQuest software (Becton Dickinson, Lincoln Pack, NJ). (C) Peritoneal macrophages were isolated 3 days after thioglycollate treatment. These cells were incubated with 0.025% fluorescent latex beads (0.75 mm) (Polyscience, Niles, IL) for 2 h. Then cells were washed vigorously 3 times with PBS to remove non-internalized beads and fixed with 2.5% formaldehyde in PBS for 20 min. Cells were monitored with Axiophot microscope (Carl Zeiss, Thornwood, NY). Left panels show Nomarski images of wild-type, and TLR4- and MyD88-deficient macrophages. Magnification x20. Fluorescent images of same cells are shown in right panels.

 
In addition to LPS from Gram-negative bacteria, Gram-positive bacterial cell wall preparations and their components, such as PGN, are known to activate host macrophages (26). Therefore, we investigated the responsiveness of mouse cells to cell wall preparation from Staphylococcus aureus and PGN from S. aureus. The cell wall preparation from S. aureus induced TNF- production in cells from wild-type mice in a dose-dependent manner. TLR4-deficient macrophages showed significant productions of TNF- in response to S. aureus cell wall, although the production was reduced compared with that of wild-type mice. In contrast, MyD88-deficient macrophages did not produce TNF- in response to any concentration of S. aureus cell wall (Fig. 3A). When stimulated with S. aureus PGN, peritoneal macrophages from TLR4-deficient mice produced TNF- in a dose-dependent manner to almost the same extent as cells from wild-type mice. In contrast, macrophages from MyD88-deficient mice did not produce TNF- at any concentration added (Fig. 3B). Mycobacterial cell wall components, e.g. lipoarabinomannan, are also known to induce activation of myeloid cells (27). We used crude whole-cell lysates from the Mycobacterium tuberculosis Aoyama B strain. Wild-type macrophages produced TNF- in response to these lysates in a dose-dependent manner. Macrophages from TLR4-deficient mice exhibited a slight defect in TNF- production compared with wild-type macrophages. In contrast, cells from MyD88-deficient mice did not produce TNF- in response to the mycobacterial crude cell lysates (Fig. 3C).

View larger version (20K): [in this window] [in a new window]   Fig. 3. Responsiveness to Gram-positive bacterial cell wall components and mycobacterial whole-cell lysates. Thioglycollate-elicited peritoneal macrophages from wild-type, and TLR4- and MyD88- deficient mice were cultured with the indicated concentrations of (A) cell wall preparation from S. aureus, (B) PGN from S. aureus, (Fluka, St Louis, MO) and (C) whole-cell lysates from M. tuberculosis Aoyama B strain for 24 h. Then, concentrations of TNF- in the culture supernatants were measured. Preparation of S. aureus cell wall was as described previously (31). Preparation of mycobacterial whole-cell lysates were as described below. M. tuberculosis Aoyama B strain (NIHJ 1635) was cultured in Dubos broth (Difco, Detroit, MI) for 1 month. Then cells were collected and resuspended with PBS. Cells were sonicated and used as mycobacterial whole-cell lysates.

 
We further examined the responses of mutant mice to other bacterial components: LPS from Escherichia coli serotype O55:B5, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium, Shigella flexneri and Vibrio cholerae, and PGN from Staphylococcus epidermidis. The responsiveness of wild-type, and TLR4- and MyD88-deficient mice to these bacterial components are summarized in Table 1. TLR4-deficient mice showed reduced, but significant responsiveness to LPS preparations from several bacterial strains. S. epidermidis PGN also induced responses in TLR4-deficient cells. In contrast, MyD88-deficient cells did not respond to any LPS or Gram-positive cell wall components. Therefore, it is likely that the recognition and signaling elicited by some LPS or Gram-positive cell wall components is mediated by TLR4 and/or other TLR that use MyD88 as an adaptor molecule.

View this table: [in this window] [in a new window]   Table 1. Responsiveness to bacterial cell wall components

 
LPS consists of an O-specific chain, a core oligosaccharide and lipid A moieties. In particular, the lipid A portion of LPS is known to be essential for its endotoxic activity (28). Lipid A from different bacterial origins has common structural similarities, but differs in such details as length of their fatty acid carbon chains and degree of phosphorylation (28). The lipid A moieties from peridontopathic pathogens such as P. gingivalis are especially unique, in that they possess unusually branched and relatively long fatty acids (15–17 carbon atoms) (25). These structural differences among LPS species may have given rise to the diversity of receptors that bind LPS. In contrast, MyD88-deficient mice were not responsive to any of the LPS samples derived from many different bacteria, indicating that all LPS receptors utilize MyD88 as an essential signaling molecule.

MyD88-deficient mice showed no response to the crude cell wall preparation and PGN derived from Gram-positive bacteria or to mycobacterial whole-cell lysates. In contrast, TLR4-deficient mice showed almost the same response to S. aureus PGN as wild-type mice, and somewhat reduced, but still significant, response to S. aureus cell wall and mycobacterial whole-cell lysates. These indicate that TLR4 may be in part responsible for the recognition of Gram-positive bacterial components and mycobacterial components. Recent studies demonstrate that TLR2 may be a signaling receptor for Gram-positive bacterial components and mycobacterial lipoproteins as well as Gram-negative LPS (21–24). Recognition of Gram-positive bacterial and mycobacterial components might be executed by at least TLR2 and TLR4. Thus, MyD88 may be essential for signaling via TLR family including TLR2 and TLR4.

In interpreting these results we had to consider the possibility of contamination of bacterial cell wall components. The bacterial component that affects the cellular response at the lowest concentration may be LPS from Gram-negative bacteria. Even if a minor component contaminated in the sample may interfere or augment the response of wild-type or TLR4-deficient mice, the fact that MyD88-deficient mice are unresponsive to all bacterial components we tested demonstrates that MyD88 is essential for the cellular response to all bacterial cell wall components.

	Acknowledgments

 
We thank Dr T. Tamura (Hyogo, Japan) for providing reagents, and Dr H. Takada (Tohoku, Japan) and Dr T. Yasui (Osaka, Japan) for helpful discussion. We thank Dr Mark Lamphier for critical reading of the manuscript. We thank T. Aoki and M. Hyuga for excellent secretarial assistance. This work was supported by grants from the Ministry of Education of Japan.

	Abbreviations

 

IL-1R IL-1 receptor

LTA lipoteichoic acid

LPS lipopolysaccharide

PGN peptidoglycan

TLR Toll-like receptor

TNF tumor necrosis factor

	Notes

 
Transmitting editor: K. Sugamura

Received 30 August 1999, accepted 8 October 1999.

	References

Top Abstract Introduction References

 

1. Medzhitov, R. and Janeway, C. A., Jr. 1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295.[Web of Science][Medline]
2. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M. and Hoffmann, J. A. 1996. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86:973.[Web of Science][Medline]
3. Hashimoto, C., Hudson, K. L. and Anderson, K. V. 1988. The Toll gene of Drosophila, required for dorsal–ventral embryonic polarity, appears to encode a transmembrane protein. Cell 52:269.[Web of Science][Medline]
4. O'Neill, L. A. and Greene, C. 1998. Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J. Leuk. Biol. 63:650.[Abstract]
5. Williams, M. J., Rodriguez, A., Kimbrell, D. A. and Eldon, E. D. 1997. The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense. EMBO J. 16:6120.[Web of Science][Medline]
6. Lemaitre, B., Reichhart, J. M. and Hoffmann, J. A. 1997. Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc. Natl Acad. Sci. USA 94:14614.[Abstract/Free Full Text]
7. Medzhitov, R., Preston-Hurlburt, P. and Janeway, C. A., Jr. 1997. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394.[Web of Science][Medline]
8. Rock, F. L., Hardiman, G., Timans, J. C., Kastelein, R. A. and Bazan, J. F. 1998. A family of human receptors structurally related to Drosophila Toll. Proc. Natl Acad. Sci. USA 95:588.[Abstract/Free Full Text]
9. Takeuchi, O., Kawai, T., Sanjo, H., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Takeda, K. and Akira, S. 1999. TLR6: a novel member of an expanding Toll-like receptor family. Gene 231:59.[Web of Science][Medline]
10. Yang, R. B., Mark, M. R., Gray, A., Huang, A., Xie, M. H., Zhang, M., Goddard, A., Wood, W. I., Gurney, A. L. and Godowski, P. J. 1998. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395:284.[Medline]
11. Kirschning, C. J., Wesche, H., Merrill Ayres, T. and Rothe, M. 1998. Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J. Exp. Med. 188:2091.[Abstract/Free Full Text]
12. Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B. and Beutler, B. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085.[Abstract/Free Full Text]
13. Qureshi, S. T., Lariviere, L., Leveque, G., Clermont, S., Moore, K. J., Gros, P. and Malo, D. 1999. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J. Exp. Med. 189:615.[Abstract/Free Full Text]
14. Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K. and Akira, S. 1999. Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J. Immunol. 162:3749.[Abstract/Free Full Text]
15. Muzio, M., Ni, J., Feng, P. and Dixit, V. M. 1997. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL- 1 signaling. Science 278:1612.[Abstract/Free Full Text]
16. Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S. and Cao, Z. 1997. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7:837.[Web of Science][Medline]
17. Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., Tsutsui, H., Sakagami, M., Nakanishi, K. and Akira, S. 1998. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL- 18-mediated function. Immunity 9:143.[Web of Science][Medline]
18. Muzio, M., Natoli, G., Saccani, S., Levrero, M. and Mantovani, A. 1998. The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J. Exp. Med. 187:2097.[Abstract/Free Full Text]
19. Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C., Ghosh, S. and Janeway, C. A., Jr. 1998. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Mol. Cell 2:253.[Web of Science][Medline]
20. Kawai, T., Adachi, O., Ogawa, T., Takeda, K. and Akira, S. 1999. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11:115.[Web of Science][Medline]
21. Schwandner, R., Dziarski, R., Wesche, H., Rothe, M. and Kirschning, C. J. 1999. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J. Biol. Chem. 274:17406.[Abstract/Free Full Text]
22. Yoshimura, A., Lien, E., Ingalls, R. R., Tuomanen, E., Dziarski, R. and Golenbock, D. 1999. Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 163:1.[Abstract/Free Full Text]
23. Brightbill, H. D., Libraty, D. H., Krutzik, S. R., Yang, R. B., Belisle, J. T., Bleharski, J. R., Maitland, M., Norgard, M. V., Plevy, S. E., Smale, S. T., Brennan, P. J., Bloom, B. R., Godowski, P. J. and Modlin, R. L. 1999. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285:732.[Abstract/Free Full Text]
24. Aliprantis, A. O., Yang, R. B., Mark, M. R., Suggett, S., Devaux, B., Radolf, J. D., Klimpel, G. R., Godowski, P. and Zychlinsky, A. 1999. Cell activation and apoptosis by bacterial lipoproteins through toll- like receptor-2. Science 285:736.[Abstract/Free Full Text]
25. Ogawa, T. 1993. Chemical structure of lipid A from 271 Porphyromonas (Bacteroides) gingivalis lipopolysaccharide. FEBS Lett. 332:197.[Web of Science][Medline]
26. Pugin, J., Heumann, I. D., Tomasz, A., Kravchenko, V. V., Akamatsu, Y., Nishijima, M., Glauser, M. P., Tobias, P. S. and Ulevitch, R. J. 1994. CD14 is a pattern recognition receptor. Immunity 1:509.[Web of Science][Medline]
27. Barnes, P. F., Chatterjee, D., Abrams, J. S., Lu, S., Wang, E., Yamamura, M., Brennan, P. J. and Modlin, R. L. 1992. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J. Immunol. 149:541.[Abstract]
28. Rietschel, E. T., Kirikae, T., Schade, F. U., Mamat, U., Schmidt, G., Loppnow, H., Ulmer, A. J., Zahringer, U., Seydel, U., Di Padova, F., et al. 1994. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 8:217.[Abstract]
30. Saito-Taki, T., Tanabe, M. J., Mochizuki, H., Nakano, M., Tsujimoto, M., Kotani, S., Yokogawa, K. and Kawata, S. 1980. Mitogenicity of cell wall preparations of gram-positive bacteria on cultured spleen cells obtained from immunologically abnormal C3H/HeJ and CBA/N-defect mice. Microbiol. Immunol. 24:249.[Web of Science][Medline]
31. Ogawa, T., Kotani, S., Fukuda, K., Tsukamoto, Y., Mori, M., Kusumoto, S. and Shiba, T. 1982. Stimulation of migration of human monocytes by bacterial cell walls and muramyl peptides. Infect. Immun. 38:817.[Abstract/Free Full Text]

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				K. Sato, K. Takahashi, M. Tohno, Y. Miura, T. Kamada, S. Ikegami, and H. Kitazawa Immunomodulation in gut-associated lymphoid tissue of neonatal chicks by immunobiotic diets Poult. Sci., December 1, 2009; 88(12): 2532 - 2538. [Abstract] [Full Text] [PDF]

				A. Tanne, B. Ma, F. Boudou, L. Tailleux, H. Botella, E. Badell, F. Levillain, M. E. Taylor, K. Drickamer, J. Nigou, et al. A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis J. Exp. Med., September 28, 2009; 206(10): 2205 - 2220. [Abstract] [Full Text] [PDF]

				C. Hall, M. V. Flores, A. Chien, A. Davidson, K. Crosier, and P. Crosier Transgenic zebrafish reporter lines reveal conserved Toll-like receptor signaling potential in embryonic myeloid leukocytes and adult immune cell lineages J. Leukoc. Biol., May 1, 2009; 85(5): 751 - 765. [Abstract] [Full Text] [PDF]

				K. L. Lloyd-Jones, M. M. Kelly, and P. Kubes Varying Importance of Soluble and Membrane CD14 in Endothelial Detection of Lipopolysaccharide J. Immunol., July 15, 2008; 181(2): 1446 - 1453. [Abstract] [Full Text] [PDF]

				T. Nyman, P. Stenmark, S. Flodin, I. Johansson, M. Hammarstrom, and P. Nordlund The Crystal Structure of the Human Toll-like Receptor 10 Cytoplasmic Domain Reveals a Putative Signaling Dimer J. Biol. Chem., May 2, 2008; 283(18): 11861 - 11865. [Abstract] [Full Text] [PDF]

				Y. Asai, Y. Makimura, A. Kawabata, and T. Ogawa Soluble CD14 Discriminates Slight Structural Differences between Lipid As That Lead to Distinct Host Cell Activation J. Immunol., December 1, 2007; 179(11): 7674 - 7683. [Abstract] [Full Text] [PDF]

				L. E. Cole, K. A. Shirey, E. Barry, A. Santiago, P. Rallabhandi, K. L. Elkins, A. C. Puche, S. M. Michalek, and S. N. Vogel Toll-Like Receptor 2-Mediated Signaling Requirements for Francisella tularensis Live Vaccine Strain Infection of Murine Macrophages Infect. Immun., August 1, 2007; 75(8): 4127 - 4137. [Abstract] [Full Text] [PDF]

				W.-F. Fang, J. H. Cho, Q. He, M.-C. Lin, C.-C. Wu, N. F. Voelkel, and I. S. Douglas Lipid A fraction of LPS induces a discrete MAPK activation in acute lung injury Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L336 - L344. [Abstract] [Full Text] [PDF]

				I. Bekeredjian-Ding, S. Inamura, T. Giese, H. Moll, S. Endres, A. Sing, U. Zahringer, and G. Hartmann Staphylococcus aureus Protein A Triggers T Cell-Independent B Cell Proliferation by Sensitizing B Cells for TLR2 Ligands J. Immunol., March 1, 2007; 178(5): 2803 - 2812. [Abstract] [Full Text] [PDF]

				J. M. Buckley, J. H. Wang, and H. P. Redmond Cellular reprogramming by gram-positive bacterial components: a review J. Leukoc. Biol., October 1, 2006; 80(4): 731 - 741. [Abstract] [Full Text] [PDF]

				S. P. Wiertsema, S.-K. Khoo, G. Baynam, R. H. Veenhoven, I. A. Laing, G. A. Zielhuis, G. T. Rijkers, J. Goldblatt, P. N. LeSouef, and E. A. M. Sanders Association of CD14 Promoter Polymorphism with Otitis Media and Pneumococcal Vaccine Responses. Clin. Vaccine Immunol., August 1, 2006; 13(8): 892 - 897. [Abstract] [Full Text] [PDF]

				J. D. Turner, R. S. Langley, K. L. Johnston, G. Egerton, S. Wanji, and M. J. Taylor Wolbachia Endosymbiotic Bacteria of Brugia malayi Mediate Macrophage Tolerance to TLR- and CD40-Specific Stimuli in a MyD88/TLR2-Dependent Manner J. Immunol., July 15, 2006; 177(2): 1240 - 1249. [Abstract] [Full Text] [PDF]

				N. Esen and T. Kielian Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns. J. Immunol., June 1, 2006; 176(11): 6802 - 6811. [Abstract] [Full Text] [PDF]

				O. A. Harari, P. Alcaide, D. Ahl, F. W. Luscinskas, and J. K. Liao Absence of TRAM Restricts Toll-Like Receptor 4 Signaling in Vascular Endothelial Cells to the MyD88 Pathway Circ. Res., May 12, 2006; 98(9): 1134 - 1140. [Abstract] [Full Text] [PDF]

				C. H. Li, J. H. Wang, and H. P. Redmond Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation J. Leukoc. Biol., April 1, 2006; 79(4): 867 - 875. [Abstract] [Full Text] [PDF]

				S. Appel, V. Mirakaj, A. Bringmann, M. M. Weck, F. Grunebach, and P. Brossart PPAR-{gamma} agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-{kappa}B pathways Blood, December 1, 2005; 106(12): 3888 - 3894. [Abstract] [Full Text] [PDF]

				K. Fuse, G. Chan, Y. Liu, P. Gudgeon, M. Husain, M. Chen, W.-C. Yeh, S. Akira, and P. P. Liu Myeloid Differentiation Factor-88 Plays a Crucial Role in the Pathogenesis of Coxsackievirus B3-Induced Myocarditis and Influences Type I Interferon Production Circulation, October 11, 2005; 112(15): 2276 - 2285. [Abstract] [Full Text] [PDF]

				C. Feterowski, A. Novotny, S. Kaiser-Moore, P. F. Muhlradt, T. Rossmann-Bloeck, M. Rump, B. Holzmann, and H. Weighardt Attenuated pathogenesis of polymicrobial peritonitis in mice after TLR2 agonist pre-treatment involves ST2 up-regulation Int. Immunol., August 1, 2005; 17(8): 1035 - 1046. [Abstract] [Full Text] [PDF]

				K. Yaraei, L. A. Campbell, X. Zhu, W. C. Liles, C.-c. Kuo, and M. E. Rosenfeld Effect of Chlamydia pneumoniae on Cellular ATP Content in Mouse Macrophages: Role of Toll-Like Receptor 2 Infect. Immun., July 1, 2005; 73(7): 4323 - 4326. [Abstract] [Full Text] [PDF]

				I. B. Bekeredjian-Ding, M. Wagner, V. Hornung, T. Giese, M. Schnurr, S. Endres, and G. Hartmann Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN J. Immunol., April 1, 2005; 174(7): 4043 - 4050. [Abstract] [Full Text] [PDF]

				R. Takii, T. Kadowaki, A. Baba, T. Tsukuba, and K. Yamamoto A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems Infect. Immun., February 1, 2005; 73(2): 883 - 893. [Abstract] [Full Text] [PDF]

				A. Q. Khan, Q. Chen, Z.-Q. Wu, J. C. Paton, and C. M. Snapper Both Innate Immunity and Type 1 Humoral Immunity to Streptococcus pneumoniae Are Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2 Infect. Immun., January 1, 2005; 73(1): 298 - 307. [Abstract] [Full Text] [PDF]

				K. Takeda and S. Akira Toll-like receptors in innate immunity Int. Immunol., January 1, 2005; 17(1): 1 - 14. [Abstract] [Full Text] [PDF]

				R. K. Pai, M. E. Pennini, A. A. R. Tobian, D. H. Canaday, W. H. Boom, and C. V. Harding Prolonged Toll-Like Receptor Signaling by Mycobacterium tuberculosis and Its 19-Kilodalton Lipoprotein Inhibits Gamma Interferon-Induced Regulation of Selected Genes in Macrophages Infect. Immun., November 1, 2004; 72(11): 6603 - 6614. [Abstract] [Full Text] [PDF]

				A. L. Eisen-Vandervelde, S. N. Waggoner, Z. Q. Yao, E. M. Cale, C. S. Hahn, and Y. S. Hahn Hepatitis C Virus Core Selectively Suppresses Interleukin-12 Synthesis in Human Macrophages by Interfering with AP-1 Activation J. Biol. Chem., October 15, 2004; 279(42): 43479 - 43486. [Abstract] [Full Text] [PDF]

				P. A. Pioli, E. Amiel, T. M. Schaefer, J. E. Connolly, C. R. Wira, and P. M. Guyre Differential Expression of Toll-Like Receptors 2 and 4 in Tissues of the Human Female Reproductive Tract Infect. Immun., October 1, 2004; 72(10): 5799 - 5806. [Abstract] [Full Text] [PDF]

				F. Hatao, M. Muroi, N. Hiki, T. Ogawa, Y. Mimura, M. Kaminishi, and K.-i. Tanamoto Prolonged Toll-like receptor stimulation leads to down-regulation of IRAK-4 protein J. Leukoc. Biol., October 1, 2004; 76(4): 904 - 908. [Abstract] [Full Text] [PDF]

				C. A. Piantadosi and D. A. Schwartz The Acute Respiratory Distress Syndrome Ann Intern Med, September 21, 2004; 141(6): 460 - 470. [Full Text] [PDF]

				M. Ueta, T. Nochi, M.-H. Jang, E. J. Park, O. Igarashi, A. Hino, S. Kawasaki, T. Shikina, T. Hiroi, S. Kinoshita, et al. Intracellularly Expressed TLR2s and TLR4s Contribution to an Immunosilent Environment at the Ocular Mucosal Epithelium J. Immunol., September 1, 2004; 173(5): 3337 - 3347. [Abstract] [Full Text] [PDF]

				C. von Meyenburg, B. H. Hrupka, D. Arsenijevic, G. J. Schwartz, R. Landmann, and W. Langhans Role for CD14, TLR2, and TLR4 in bacterial product-induced anorexia Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R298 - R305. [Abstract] [Full Text] [PDF]

				S. Epelman, D. Stack, C. Bell, E. Wong, G. G. Neely, S. Krutzik, K. Miyake, P. Kubes, L. D. Zbytnuik, L. L. Ma, et al. Different Domains of Pseudomonas aeruginosa Exoenzyme S Activate Distinct TLRs J. Immunol., August 1, 2004; 173(3): 2031 - 2040. [Abstract] [Full Text] [PDF]

				N. Liu, R. R. Montgomery, S. W. Barthold, and L. K. Bockenstedt Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice Infect. Immun., June 1, 2004; 72(6): 3195 - 3203. [Abstract] [Full Text] [PDF]

				A. G. Rothfuchs, C. Trumstedt, H. Wigzell, and M. E. Rottenberg Intracellular Bacterial Infection-Induced IFN-{gamma} Is Critically but Not Solely Dependent on Toll-Like Receptor 4-Myeloid Differentiation Factor 88-IFN-{alpha}{beta}-STAT1 Signaling J. Immunol., May 15, 2004; 172(10): 6345 - 6353. [Abstract] [Full Text] [PDF]

				J. Branger, J. C. Leemans, S. Florquin, S. Weijer, P. Speelman, and T. van der Poll Toll-like receptor 4 plays a protective role in pulmonary tuberculosis in mice Int. Immunol., March 1, 2004; 16(3): 509 - 516. [Abstract] [Full Text] [PDF]

				T. J. Murphy, H. M. Paterson, J. A. Mannick, and J. A. Lederer Injury, sepsis, and the regulation of Toll-like receptor responses J. Leukoc. Biol., March 1, 2004; 75(3): 400 - 407. [Abstract] [Full Text] [PDF]

				J.-L. Imler and L. Zheng Biology of Toll receptors: lessons from insects and mammals J. Leukoc. Biol., January 1, 2004; 75(1): 18 - 26. [Abstract] [Full Text] [PDF]

				M. Boes, N. Bertho, J. Cerny, M. Op den Brouw, T. Kirchhausen, and H. Ploegh T Cells Induce Extended Class II MHC Compartments in Dendritic Cells in a Toll-Like Receptor-Dependent Manner J. Immunol., October 15, 2003; 171(8): 4081 - 4088. [Abstract] [Full Text] [PDF]

				K. A. Fitzgerald, D. C. Rowe, B. J. Barnes, D. R. Caffrey, A. Visintin, E. Latz, B. Monks, P. M. Pitha, and D. T. Golenbock LPS-TLR4 Signaling to IRF-3/7 and NF-{kappa}B Involves the Toll Adapters TRAM and TRIF J. Exp. Med., October 6, 2003; 198(7): 1043 - 1055. [Abstract] [Full Text] [PDF]

				S. Akira Toll-like Receptor Signaling J. Biol. Chem., October 3, 2003; 278(40): 38105 - 38108. [Full Text] [PDF]

				M. d. J. Arana, M. G. Vallespi, G. Chinea, G. V. Vallespi, I. Rodriguez-Alonso, H. E. Garay, W. A. Buurman, and O. Reyes Inhibition of LPS-responses by synthetic peptides derived from LBP associates with the ability of the peptides to block LBP-LPS interaction Innate Immunity, October 1, 2003; 9(5): 281 - 291. [Abstract] [PDF]

				A. Kariyone, T. Tamura, H. Kano, Y. Iwakura, K. Takeda, S. Akira, and K. Takatsu Immunogenicity of Peptide-25 of Ag85B in Th1 development: role of IFN-{gamma} Int. Immunol., October 1, 2003; 15(10): 1183 - 1194. [Abstract] [Full Text] [PDF]

				M. Fujita, T. Into, M. Yasuda, T. Okusawa, S. Hamahira, Y. Kuroki, A. Eto, T. Nisizawa, M. Morita, and K.-i. Shibata Involvement of Leucine Residues at Positions 107, 112, and 115 in a Leucine-Rich Repeat Motif of Human Toll-Like Receptor 2 in the Recognition of Diacylated Lipoproteins and Lipopeptides and Staphylococcus aureus Peptidoglycans J. Immunol., October 1, 2003; 171(7): 3675 - 3683. [Abstract] [Full Text] [PDF]

				K. A. Marr, S. Arunmozhi Balajee, T. R. Hawn, A. Ozinsky, U. Pham, S. Akira, A. Aderem, and W. Conrad Liles Differential Role of MyD88 in Macrophage-Mediated Responses to Opportunistic Fungal Pathogens Infect. Immun., September 1, 2003; 71(9): 5280 - 5286. [Abstract] [Full Text] [PDF]

				N. Mori, A. M. Krensky, R. Geleziunas, A. Wada, T. Hirayama, C. Sasakawa, and N. Yamamoto Helicobacter pylori Induces RANTES through Activation of NF-{kappa}B Infect. Immun., July 1, 2003; 71(7): 3748 - 3756. [Abstract] [Full Text] [PDF]

				A. Pivarcsi, L. Bodai, B. Rethi, A. Kenderessy-Szabo, A. Koreck, M. Szell, Z. Beer, Z. Bata-Csorgoo, M. Magocsi, E. Rajnavolgyi, et al. Expression and function of Toll-like receptors 2 and 4 in human keratinocytes Int. Immunol., June 1, 2003; 15(6): 721 - 730. [Abstract] [Full Text] [PDF]

				C. F. Ortega-Cava, S. Ishihara, M. A. K. Rumi, K. Kawashima, N. Ishimura, H. Kazumori, J. Udagawa, Y. Kadowaki, and Y. Kinoshita Strategic Compartmentalization of Toll-Like Receptor 4 in the Mouse Gut J. Immunol., April 15, 2003; 170(8): 3977 - 3985. [Abstract] [Full Text] [PDF]

				E. Muraille, C. De Trez, M. Brait, P. De Baetselier, O. Leo, and Y. Carlier Genetically Resistant Mice Lacking MyD88-Adapter Protein Display a High Susceptibility to Leishmania major Infection Associated with a Polarized Th2 Response J. Immunol., April 15, 2003; 170(8): 4237 - 4241. [Abstract] [Full Text] [PDF]

				T. Ogawa, Y. Asai, M. Hashimoto, O. Takeuchi, T. Kurita, Y. Yoshikai, K. Miyake, and S. Akira Cell activation by Porphyromonas gingivalis lipid A molecule through Toll-like receptor 4- and myeloid differentiation factor 88-dependent signaling pathway Int. Immunol., November 1, 2002; 14(11): 1325 - 1332. [Abstract] [Full Text] [PDF]

				M. A. Wolfert, T. F. Murray, G.-J. Boons, and J. N. Moore The Origin of the Synergistic Effect of Muramyl Dipeptide with Endotoxin and Peptidoglycan J. Biol. Chem., October 11, 2002; 277(42): 39179 - 39186. [Abstract] [Full Text] [PDF]

				H. Takada, S. Yokoyama, and Shuhua Yang Mini-review: Enhancement of endotoxin activity by muramyldipeptide Innate Immunity, October 1, 2002; 8(5): 337 - 342. [Abstract] [PDF]

				N. Reiling, C. Holscher, A. Fehrenbach, S. Kroger, C. J. Kirschning, S. Goyert, and S. Ehlers Cutting Edge: Toll-Like Receptor (TLR)2- and TLR4-Mediated Pathogen Recognition in Resistance to Airborne Infection with Mycobacterium tuberculosis J. Immunol., October 1, 2002; 169(7): 3480 - 3484. [Abstract] [Full Text] [PDF]

				B. T. Edelson and E. R. Unanue MyD88-Dependent but Toll-Like Receptor 2-Independent Innate Immunity to Listeria: No Role for Either in Macrophage Listericidal Activity J. Immunol., October 1, 2002; 169(7): 3869 - 3875. [Abstract] [Full Text] [PDF]

				B. Billack, D. E. Heck, T. M. Mariano, C. R. Gardner, R. Sur, D. L. Laskin, and J. D. Laskin Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and endothelial cells Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1267 - C1277. [Abstract] [Full Text] [PDF]

				H. Weighardt, S. Kaiser-Moore, R. M. Vabulas, C. J. Kirschning, H. Wagner, and B. Holzmann Cutting Edge: Myeloid Differentiation Factor 88 Deficiency Improves Resistance Against Sepsis Caused by Polymicrobial Infection J. Immunol., September 15, 2002; 169(6): 2823 - 2827. [Abstract] [Full Text] [PDF]

				S. E. Applequist, R. P. A. Wallin, and H.-G. Ljunggren Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines Int. Immunol., September 1, 2002; 14(9): 1065 - 1074. [Abstract] [Full Text] [PDF]

				N. Tsuboi, Y. Yoshikai, S. Matsuo, T. Kikuchi, K.-I. Iwami, Y. Nagai, O. Takeuchi, S. Akira, and T. Matsuguchi Roles of Toll-Like Receptors in C-C Chemokine Production by Renal Tubular Epithelial Cells J. Immunol., August 15, 2002; 169(4): 2026 - 2033. [Abstract] [Full Text] [PDF]

				A. UEHARA, S. SUGAWARA, and H. TAKADA Priming of human oral epithelial cells by interferon-{gamma} to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans J. Med. Microbiol., August 1, 2002; 51(8): 626 - 634. [Abstract] [Full Text] [PDF]

				T. Wang, W. P. Lafuse, K. Takeda, S. Akira, and B. S. Zwilling Rapid Chromatin Remodeling of Toll-Like Receptor 2 Promoter During Infection of Macrophages with Mycobacterium avium J. Immunol., July 15, 2002; 169(2): 795 - 801. [Abstract] [Full Text] [PDF]

				S. Sato, O. Takeuchi, T. Fujita, H. Tomizawa, K. Takeda, and S. Akira A variety of microbial components induce tolerance to lipopolysaccharide by differentially affecting MyD88-dependent and -independent pathways Int. Immunol., July 1, 2002; 14(7): 783 - 791. [Abstract] [Full Text] [PDF]

				R. Tamai, T. Sakuta, K. Matsushita, M. Torii, O. Takeuchi, S. Akira, S. Akashi, T. Espevik, S. Sugawara, and H. Takada Human Gingival CD14+ Fibroblasts Primed with Gamma Interferon Increase Production of Interleukin-8 in Response to Lipopolysaccharide through Up-Regulation of Membrane CD14 and MyD88 mRNA Expression Infect. Immun., March 1, 2002; 70(3): 1272 - 1278. [Abstract] [Full Text] [PDF]

				S. Epelman, G. G. Neely, L. L. Ma, M. Gjomarkaj, E. Pace, M. Melis, D. E. Woods, and C. H. Mody Distinct fates of monocytes and T cells directly activated by Pseudomonas aeruginosa exoenzyme S J. Leukoc. Biol., March 1, 2002; 71(3): 458 - 468. [Abstract] [Full Text] [PDF]

				D. A. Schwartz The Genetics of Innate Immunity Chest, March 1, 2002; 121 (2009): 62S - 68S. [Abstract] [Full Text] [PDF]

				X. Wang, C. Moser, J.-P. Louboutin, E. S. Lysenko, D. J. Weiner, J. N. Weiser, and J. M. Wilson Toll-Like Receptor 4 Mediates Innate Immune Responses to Haemophilus influenzae Infection in Mouse Lung J. Immunol., January 15, 2002; 168(2): 810 - 815. [Abstract] [Full Text] [PDF]

				C. Termeer, F. Benedix, J. Sleeman, C. Fieber, U. Voith, T. Ahrens, K. Miyake, M. Freudenberg, C. Galanos, and J. C. Simon Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4 J. Exp. Med., January 7, 2002; 195(1): 99 - 111. [Abstract] [Full Text] [PDF]

				E. Cario, D. Brown, M. McKee, K. Lynch-Devaney, G. Gerken, and D. K. Podolsky Commensal-Associated Molecular Patterns Induce Selective Toll-Like Receptor-Trafficking from Apical Membrane to Cytoplasmic Compartments in Polarized Intestinal Epithelium Am. J. Pathol., January 1, 2002; 160(1): 165 - 173. [Abstract] [Full Text] [PDF]

				J. D. McCurdy, T.-J. Lin, and J. S. Marshall Toll-like receptor 4-mediated activation of murine mast cells J. Leukoc. Biol., December 1, 2001; 70(6): 977 - 984. [Abstract] [Full Text] [PDF]

				S. Prebeck, C. Kirschning, S. Durr, C. da Costa, B. Donath, K. Brand, V. Redecke, H. Wagner, and T. Miethke Predominant Role of Toll-Like Receptor 2 Versus 4 in Chlamydia pneumoniae-Induced Activation of Dendritic Cells J. Immunol., September 15, 2001; 167(6): 3316 - 3323. [Abstract] [Full Text] [PDF]

				V. Supajatura, H. Ushio, A. Nakao, K. Okumura, C. Ra, and H. Ogawa Protective Roles of Mast Cells Against Enterobacterial Infection Are Mediated by Toll-Like Receptor 4 J. Immunol., August 15, 2001; 167(4): 2250 - 2256. [Abstract] [Full Text] [PDF]

				S. Sugawara, S. Yang, K. Iki, J. Hatakeyama, R. Tamai, O. Takeuchi, S. Akashi, T. Espevik, S. Akira, and H. Takada Monocytic Cell Activation by Nonendotoxic Glycoprotein from Prevotella intermedia ATCC 25611 Is Mediated by Toll-Like Receptor 2 Infect. Immun., August 1, 2001; 69(8): 4951 - 4957. [Abstract] [Full Text] [PDF]

				C. Alexander and E. Th. Rietschel Invited review: Bacterial lipopolysaccharides and innate immunity Innate Immunity, June 1, 2001; 7(3): 167 - 202. [Abstract] [PDF]

				T. Kaisho, O. Takeuchi, T. Kawai, K. Hoshino, and S. Akira Endotoxin-Induced Maturation of MyD88-Deficient Dendritic Cells J. Immunol., May 1, 2001; 166(9): 5688 - 5694. [Abstract] [Full Text] [PDF]

				S. Yang, R. Tamai, S. Akashi, O. Takeuchi, S. Akira, S. Sugawara, and H. Takada Synergistic Effect of Muramyldipeptide with Lipopolysaccharide or Lipoteichoic Acid To Induce Inflammatory Cytokines in Human Monocytic Cells in Culture Infect. Immun., April 1, 2001; 69(4): 2045 - 2053. [Abstract] [Full Text] [PDF]

				Q. Wang, R. Dziarski, C. J. Kirschning, M. Muzio, and D. Gupta Micrococci and Peptidoglycan Activate TLR2{right-arrow}MyD88{right-arrow}IRAK{right-arrow}TRAF{right-arrow}NIK{right-arrow}IKK{right-arrow}NF-{kappa}B Signal Transduction Pathway That Induces Transcription of Interleukin-8 Infect. Immun., April 1, 2001; 69(4): 2270 - 2276. [Abstract] [Full Text] [PDF]

				T. K. Means, B. W. Jones, A. B. Schromm, B. A. Shurtleff, J. A. Smith, J. Keane, D. T. Golenbock, S. N. Vogel, and M. J. Fenton Differential Effects of a Toll-Like Receptor Antagonist on Mycobacterium tuberculosis-Induced Macrophage Responses J. Immunol., March 15, 2001; 166(6): 4074 - 4082. [Abstract] [Full Text] [PDF]

				E. Seki, H. Tsutsui, H. Nakano, N. M. Tsuji, K. Hoshino, O. Adachi, K. Adachi, S. Futatsugi, K. Kuida, O. Takeuchi, et al. Lipopolysaccharide-Induced IL-18 Secretion from Murine Kupffer Cells Independently of Myeloid Differentiation Factor 88 That Is Critically Involved in Induction of Production of IL-12 and IL-1{{beta}} J. Immunol., February 15, 2001; 166(4): 2651 - 2657. [Abstract] [Full Text] [PDF]

				R. Dziarski, Q. Wang, K. Miyake, C. J. Kirschning, and D. Gupta MD-2 Enables Toll-Like Receptor 2 (TLR2)-Mediated Responses to Lipopolysaccharide and Enhances TLR2-Mediated Responses to Gram-Positive and Gram-Negative Bacteria and Their Cell Wall Components J. Immunol., February 1, 2001; 166(3): 1938 - 1944. [Abstract] [Full Text] [PDF]

				S. Sato, F. Nomura, T. Kawai, O. Takeuchi, P. F. Muhlradt, K. Takeda, and S. Akira Synergy and Cross-Tolerance Between Toll-Like Receptor (TLR) 2- and TLR4-Mediated Signaling Pathways J. Immunol., December 15, 2000; 165(12): 7096 - 7101. [Abstract] [Full Text] [PDF]

				A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors PNAS, November 22, 2000; (2000) 250476497. [Abstract] [Full Text]

				O. Takeuchi, K. Hoshino, and S. Akira Cutting Edge: TLR2-Deficient and MyD88-Deficient Mice Are Highly Susceptible to Staphylococcus aureus Infection J. Immunol., November 15, 2000; 165(10): 5392 - 5396. [Abstract] [Full Text] [PDF]

				S. Akira, K. Hoshino, and T. Kaisho The role of Toll-like receptors and MyD88 in innate immune responses Innate Immunity, October 1, 2000; 6(5): 383 - 387. [Abstract] [PDF]

				N. W. J. Schroder, B. Opitz, N. Lamping, K. S. Michelsen, U. Zahringer, U. B. Gobel, and R. R. Schumann Involvement of Lipopolysaccharide Binding Protein, CD14, and Toll-Like Receptors in the Initiation of Innate Immune Responses by Treponema Glycolipids J. Immunol., September 1, 2000; 165(5): 2683 - 2693. [Abstract] [Full Text] [PDF]

				R. M. Vabulas, P. Ahmad-Nejad, C. da Costa, T. Miethke, C. J. Kirschning, H. Hacker, and H. Wagner Endocytosed HSP60s Use Toll-like Receptor 2 (TLR2) and TLR4 to Activate the Toll/Interleukin-1 Receptor Signaling Pathway in Innate Immune Cells J. Biol. Chem., August 10, 2001; 276(33): 31332 - 31339. [Abstract] [Full Text] [PDF]

				S. Maeda, M. Akanuma, Y. Mitsuno, Y. Hirata, K. Ogura, H. Yoshida, Y. Shiratori, and M. Omata Distinct Mechanism of Helicobacter pylori-mediated NF-kappa B Activation between Gastric Cancer Cells and Monocytic Cells J. Biol. Chem., November 21, 2001; 276(48): 44856 - 44864. [Abstract] [Full Text] [PDF]

				A. Ozinsky, D. M. Underhill, J. D. Fontenot, A. M. Hajjar, K. D. Smith, C. B. Wilson, L. Schroeder, and A. Aderem The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors PNAS, December 5, 2000; 97(25): 13766 - 13771. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (158) Request Permissions Google Scholar Articles by Takeuchi, O. Articles by Akira, S. Search for Related Content PubMed PubMed Citation Articles by Takeuchi, O. Articles by Akira, S. Social Bookmarking          What's this?

Online ISSN 1460-2377 - Print ISSN 0953-8178

Copyright © 2009 Japanese Society for Immunology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics