Toll-like receptor 2-deficient mice succumb to Mycobacterium tuberculosis infection.
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.
Drennan
Michael B
MB
Department of Immunology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. mdrennan@uctgsh1.uct.ac.za
Nicolle
Delphine
D
Quesniaux
Valerie J F
VJ
Jacobs
Muazzam
M
Allie
Nasiema
N
Mpagi
Joseph
J
Frémond
Cécile
C
Wagner
Hermann
H
Kirschning
Carsten
C
Ryffel
Bernhard
B
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*
D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors