Increased resistance to mycobacterial infection in the absence of interleukin-10.
Interleukin-10 (IL-10) down-regulates T helper type 1 cell and macrophage functions. As IL-10 is induced along with tumour necrosis factor (TNF) and IL-12 in mycobacterial infection, we asked whether endogenous IL-10 plays a role in the antimycobacterial response. We demonstrate here that IL-10-deficient mice eliminate Mycobacterium bovis Calmette-Guérin bacillus faster than wild-type mice. Granulomas are significantly larger, containing more CD-11b- and CD11c-positive antigen-presenting cells and T cells, and the expression of major histocompatibility complex class II and intracellular adhesion molecule-1 is increased. Macrophages in granulomas of IL-10-deficient mice express high levels of TNF, acid phosphatase and inducible nitric oxide synthase (iNOS). Finally, an increased cutaneous delayed-type hypersensitivity reaction to mycobacterial proteins is further evidence of an augmented cell-mediated immune response. In conclusion, the cell-mediated immunity is enhanced in the absence of IL-10, resulting in a robust granuloma response, which accelerates the clearance of mycobacteria. Therefore, endogenous IL-10 attenuates mycobacterial immunity.
Department of Immunology, University of Cape Town, South Africa.
M
M
Jacobs
N
N
Brown
N
N
Allie
R
R
Gulert
B
B
Ryffel
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006099:Granuloma / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
D016207:Cytokines; D014373:Tuberculin; D016753:Interleukin-10