title: Increased susceptibility of mice lacking T-bet to infection with Mycobacterium tuberculosis correlates with increased IL-10 and decreased IFN-gamma production.
abstract: 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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Sullivan
authors.forename: Ousman
authors.initials: O
authors.lastname: Jobe
authors.forename: Vanja
authors.initials: V
authors.lastname: Lazarevic
authors.forename: Kristine
authors.initials: K
authors.lastname: Vasquez
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: Igor
authors.initials: I
authors.lastname: Kramnik
mesh_terms: 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
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D016753:Interleukin-10; D007371:Interferon-gamma