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Cutting Edge |
* Division of Molecular Infection Biology, Research Center Borstel, Borstel, Germany;
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Munich, Germany; and
Division of Molecular Medicine, Cornell University Medical College, Manhasset, NY 11030
Innate resistance against Mycobacterium tuberculosis is thought to depend critically on engagement of pattern recognition receptors on macrophages. However, the relative contribution of these receptors for containing M. tuberculosis infection has remained unexplored in vivo. To address this issue, we infected mice defective in CD14, TLR2, or TLR4 with M. tuberculosis by aerosol. Following infection with 100 mycobacteria, either mutant strain was as resistant as congenic control mice. Granuloma formation, macrophage activation, and secretion of proinflammatory cytokines in response to low-dose aerosol infection were identical in mutant and control mice. However, high-dose aerosol challenge with 2000 CFU M. tuberculosis revealed TLR2-, but not TLR4-defective mice to be more susceptible than control mice. In conclusion, while TLR2 signaling contributes to innate resistance against M. tuberculosis in borderline situations, its function, and that of CD14 and TLR4, in initiating protective responses against naturally low-dose airborne infection is redundant.
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L. E. Yauch, M. K. Mansour, S. Shoham, J. B. Rottman, and S. M. Levitz Involvement of CD14, Toll-Like Receptors 2 and 4, and MyD88 in the Host Response to the Fungal Pathogen Cryptococcus neoformans In Vivo Infect. Immun., September 1, 2004; 72(9): 5373 - 5382. [Abstract] [Full Text] [PDF]
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S. Jang, S. Uematsu, S. Akira, and P. Salgame IL-6 and IL-10 Induction from Dendritic Cells in Response to Mycobacterium tuberculosis Is Predominantly Dependent on TLR2-Mediated Recognition J. Immunol., September 1, 2004; 173(5): 3392 - 3397. [Abstract] [Full Text] [PDF]
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N. W. Brattig, C. Bazzocchi, C. J. Kirschning, N. Reiling, D. W. Buttner, F. Ceciliani, F. Geisinger, H. Hochrein, M. Ernst, H. Wagner, et al. The Major Surface Protein of Wolbachia Endosymbionts in Filarial Nematodes Elicits Immune Responses through TLR2 and TLR4 J. Immunol., July 1, 2004; 173(1): 437 - 445. [Abstract] [Full Text] [PDF]
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A. Bafica, C. A. Scanga, M. Schito, D. Chaussabel, and A. Sher Influence of Coinfecting Pathogens on HIV Expression: Evidence for a Role of Toll-Like Receptors J. Immunol., June 15, 2004; 172(12): 7229 - 7234. [Abstract] [Full Text] [PDF]
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A. Vazquez-Torres, B. A. Vallance, M. A. Bergman, B. B. Finlay, B. T. Cookson, J. Jones-Carson, and F. C. Fang Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity to Salmonella: Importance of the Kupffer Cell Network J. Immunol., May 15, 2004; 172(10): 6202 - 6208. [Abstract] [Full Text] [PDF]
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C. A. Scanga, A. Bafica, C. G. Feng, A. W. Cheever, S. Hieny, and A. Sher MyD88-Deficient Mice Display a Profound Loss in Resistance to Mycobacterium tuberculosis Associated with Partially Impaired Th1 Cytokine and Nitric Oxide Synthase 2 Expression Infect. Immun., April 1, 2004; 72(4): 2400 - 2404. [Abstract] [Full Text] [PDF]
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S. C. Derrick, C. Repique, P. Snoy, A. L. Yang, and S. Morris Immunization with a DNA Vaccine Cocktail Protects Mice Lacking CD4 Cells against an Aerogenic Infection with Mycobacterium tuberculosis Infect. Immun., March 1, 2004; 72(3): 1685 - 1692. [Abstract] [Full Text] [PDF]
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 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]
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J. L. Coleman and J. L. Benach The Urokinase Receptor Can Be Induced by Borrelia burgdorferi through Receptors of the Innate Immune System Infect. Immun., October 1, 2003; 71(10): 5556 - 5564. [Abstract] [Full Text] [PDF]
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K. A. Heldwein, M. D. Liang, T. K. Andresen, K. E. Thomas, A. M. Marty, N. Cuesta, S. N. Vogel, and M. J. Fenton TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG J. Leukoc. Biol., August 1, 2003; 74(2): 277 - 286. [Abstract] [Full Text] [PDF]
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A. Bafica, C. A. Scanga, M. L. Schito, S. Hieny, and A. Sher Cutting Edge: In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2 J. Immunol., August 1, 2003; 171(3): 1123 - 1127. [Abstract] [Full Text] [PDF]
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M. Martin, R. E. Schifferle, N. Cuesta, S. N. Vogel, J. Katz, and S. M. Michalek Role of the Phosphatidylinositol 3 Kinase-Akt Pathway in the Regulation of IL-10 and IL-12 by Porphyromonas gingivalis Lipopolysaccharide J. Immunol., July 15, 2003; 171(2): 717 - 725. [Abstract] [Full Text] [PDF]
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A. B. Kamath, J. Alt, H. Debbabi, and S. M. Behar Toll-Like Receptor 4-Defective C3H/HeJ Mice Are Not More Susceptible than Other C3H Substrains to Infection with Mycobacterium tuberculosis Infect. Immun., July 1, 2003; 71(7): 4112 - 4118. [Abstract] [Full Text] [PDF]
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