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International Immunology, Vol. 16, No. 3, pp. 509-516, March 2004
© 2004 Japanese Society for Immunology

Toll-like receptor 4 plays a protective role in pulmonary tuberculosis in mice

Judith Branger1,2, Jaklien C. Leemans1, Sandrine Florquin2, Sebastiaan Weijer1, Peter Speelman1,3 and Tom van der Poll1,3

1 Department of Experimental Internal Medicine, 2 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS and 3 Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Correspondence to: J. Branger, Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Room G2-105, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: j.branger{at}amc.uva.nl
Transmitting editor: K. Yamamoto

Toll-like receptors (TLR) play an essential role in the innate recognition of microorganisms by the host. To determine the role of TLR4 in host defense against lung tuberculosis, TLR4 mutant (C3H/HeJ) and wild-type (C3H/HeN) mice were intranasally infected with live Mycobacterium tuberculosis. TLR4 mutant mice were more susceptible to pulmonary tuberculosis, as indicated by a reduced survival and an enhanced mycobacterial outgrowth. Lung infiltrates were more profound in TLR4 mutant mice and contained more activated T cells. Splenocytes of infected TLR4 mutant mice demonstrated a reduced capacity to produce the protective type 1 cytokine IFN-{gamma} upon antigen-specific stimulation, indicating that TLR4 may be involved in the generation of acquired T cell-mediated immunity. These data suggest that TLR4 plays a protective role in host defense against lung infection by M. tuberculosis.

Keywords: inflammation, innate host defense, mice, Mycobacterium tuberculosis, TLR4


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