title: Enhanced immune response in Mycobacterium bovis bacille calmette guerin (BCG)-infected IL-10-deficient mice.
abstract: The role of the endogenous interleukin-10 (IL-10) in the control of Mycobacterium bovis Bacille Calmette Guerin (BCG) infection was assessed using IL-10-deficient (IL-10-/-) mice. Similar to wild-type (WT) mice, IL-10-/- mice were resistant to intravenous challenge with Mycobacterium bovis BCG. Significantly higher plasma concentrations of IL-12 and tumour necrosis factor (TNF) indicated an elevated protective immune response of IL-10-/- mice. Determination of bacilli burden in IL-10-/- mice showed accelerated clearance in the lungs, spleen and the liver in comparison to WT mice. Enhanced inflammation and a vigorous granulomatous response accompanied accelerated mycobacterial clearance. Immunohistochemical analysis of hepatic granulomas from IL-10-/- mice revealed augmented lymphocyte recruitment and macrophage activation, such as increased major histocompatibility complex (MHC) class II and inducible nitric oxide synthase (iNOS) expression. Further, it was found that enlarged granulomas persisted subsequent to mycobacterial clearance and failed to resolve in the absence of IL-10. In conclusion, endogenous IL-10 dampens the cell-mediated immune response to mycobacterial infection.
authors.affiliation: Department of Immunology, University of Cape Town, South Africa. mjacobs@uctgsh1.uct.ac.za
authors.forename: Muazzam
authors.initials: M
authors.lastname: Jacobs
authors.forename: Lizette
authors.initials: L
authors.lastname: Fick
authors.forename: Nasiema
authors.initials: N
authors.lastname: Allie
authors.forename: Najmeeyah
authors.initials: N
authors.lastname: Brown
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006099:Granuloma / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood; D008262:Macrophage Activation / Q000502:physiology; D051379:Mice; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D009929:Organ Size; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12