title: Toll-like receptor 2-deficient mice succumb to Mycobacterium tuberculosis infection.
abstract: Recognition of Mycobacterium tuberculosis by the innate immune system is essential in the development of an adaptive immune response. Mycobacterial cell wall components activate macrophages through Toll-like receptor (TLR) 2, suggesting that this innate immune receptor plays a role in the host response to M. tuberculosis infection. After aerosol infection with either 100 or 500 live mycobacteria, TLR2-deficient mice display reduced bacterial clearance, a defective granulomatous response, and develop chronic pneumonia. Analysis of pulmonary immune responses in TLR2-deficient mice after 500 mycobacterial aerosol challenge showed increased levels of interferon-gamma, tumor necrosis factor-alpha, and interleukin-12p40 as well as increased numbers of CD4(+) and CD8(+) cells. Furthermore, TLR2-deficient mice mounted elevated Ag-specific type 1 T-cell responses that were not protective because all deficient mice succumb to infection within 5 months. Taken together, the data suggests that TLR2 may function as a regulator of inflammation, and in its absence an exaggerated immune inflammatory response develops.
authors.affiliation: Department of Immunology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. mdrennan@uctgsh1.uct.ac.za
authors.forename: Michael B
authors.initials: MB
authors.lastname: Drennan
authors.forename: Delphine
authors.initials: D
authors.lastname: Nicolle
authors.forename: Valerie J F
authors.initials: VJ
authors.lastname: Quesniaux
authors.forename: Muazzam
authors.initials: M
authors.lastname: Jacobs
authors.forename: Nasiema
authors.initials: N
authors.lastname: Allie
authors.forename: Joseph
authors.initials: J
authors.lastname: Mpagi
authors.forename: Cécile
authors.initials: C
authors.lastname: Frémond
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Carsten
authors.initials: C
authors.lastname: Kirschning
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000276:immunology*; D051379:Mice; D009169:Mycobacterium tuberculosis; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors