Cutting edge: IFN-gamma regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection.
T cell responses are important to the control of infection but are deleterious if not regulated. IFN-gamma-deficient mice infected with mycobacteria exhibit enhanced accumulation of activated effector T cells and neutrophils within granulomatous lesions. These cells do not control bacterial growth and compromise the integrity of the infected tissue. We show that IFN-gamma-deficient mice have increased numbers of IL-17-producing T cells following infection with Mycobacterium bovis bacille Calmette Guérin. Furthermore, exogenous IFN-gamma increases IL-12 and decreases IL-23 production by bacille Calmette Guérin-infected bone marrow-derived dendritic cells and reduces the frequency of IL-17-producing T cells induced by these bone marrow-derived dendritic cells. These data support the hypothesis that, during mycobacterial infection, both IFN-gamma- and IL-17-producing T cells are induced, but that IFN-gamma serves to limit the IL-17-producing T cell population. This counterregulation pathway may be an important factor in limiting mycobacterially associated immune-mediated pathology.
Cruz
Andrea
A
Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
Khader
Shabaana A
SA
Torrado
Egidio
E
Fraga
Alexandra
A
Pearl
John E
JE
Pedrosa
Jorge
J
Cooper
Andrea M
AM
Castro
António G
AG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006131:Growth Inhibitors / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009163:Mycobacterium bovis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology
D006131:Growth Inhibitors; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018664:Interleukin-12; D007371:Interferon-gamma