Increased susceptibility of mice lacking T-bet to infection with Mycobacterium tuberculosis correlates with increased IL-10 and decreased IFN-gamma production.
A sustained CD4+ Th1-dominated type 1 immune response is required to successfully control Mycobacterium tuberculosis infection. Considerable work has demonstrated that the transcription factor, T-bet, is required for IFN-gamma expression and fundamental to the generation of type 1 immunity in multiple cell types. Mice lacking T-bet are susceptible to virulent M. tuberculosis infection. Susceptibility of T-bet-deficient mice is associated with increased systemic bacterial burden, diminished IFN-gamma production, and the striking accumulation of eosinophilic macrophages and multinucleated giant cells in the lung. Interestingly, T-bet(-/-) mice did not develop a fully polarized Th2 response toward M. tuberculosis, but exhibited selective elevation of IL-10 production. These results indicate that T-bet plays a central role in controlling M. tuberculosis disease progression, in part through the regulation of both IFN-gamma and IL-10.
Sullivan
Brandon M
BM
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Jobe
Ousman
O
Lazarevic
Vanja
V
Vasquez
Kristine
K
Bronson
Roderick
R
Glimcher
Laurie H
LH
Kramnik
Igor
I
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015744:Giant Cells, Langhans / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D016753:Interleukin-10; D007371:Interferon-gamma