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International Immunology Advance Access originally published online on April 7, 2008
International Immunology 2008 20(5):709-718; doi:10.1093/intimm/dxn027
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Cross-talk among Toll-like receptors and their ligands

Marco Palazzo1, Silvia Gariboldi1, Laura Zanobbio2, Giuseppina F. Dusio1, Silvia Selleri1, Marzia Bedoni1, Andrea Balsari2,3 and Cristiano Rumio1

1 Department of Human Morphology
2 Institute of Pathology, Università degli Studi di Milano, via Mangiagalli 31, 20133 Milan, Italy
3 Department of Experimental Oncology Fondazione IRCCS, Istituto Nazionale Dei Tumori, via Venezian 1, 20133 Milan, Italy

Correspondence to: C. Rumio; E-mail: cristiano.rumio{at}unimi.it

Toll-like receptors (TLRs) 4, 5, 7 and 9 belong to a family of proteins that recognize mainly conserved microbial motifs. Though each TLR has a highly specific ability to recognize a particular microbial pattern, recent papers suggest that some ligands are able to affect the expression of different TLRs. In this paper, we have investigated TLR4, 5, 7 and 9 expression, both at mRNA and protein level, following treatment of different intestinal epithelial cell lines with LPS, flagellin, loxiribine, CpG-oligodeoxynucleotide and peptidoglycan, to assess if the different TLR ligands may modulate the expression of the respective TLR and of the unrelated ones. Our results show that a cross-talk exists between TLRs and various ligands, indicating a cross-regulation among these pattern recognition receptors. In particular, TLR4 was generally down-regulated by treatment with ligands other than LPS, while flagellin and unrelated microbial-associated molecular patterns exerted a general stimulatory activity as regards TLR5 expression. Concerning TLR7 and 9, we have observed a more variable behaviour of the various cell lines with the different ligands. Together, our results demonstrate that the expression of TLRs in intestinal cells is highly dynamic and tightly regulated in response to encountered microbial stimuli.

Keywords: CpG-ODN, flagellin, loxiribine, LPS, peptidoglycan

Transmitting editor: G. Trinchieri

Received 27 November 2007, accepted 19 February 2008.


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