title: Interleukin-12p70-dependent interferon- gamma production is crucial for resistance in African trypanosomiasis.
abstract: African trypanosomiasis encompasses diseases caused by pathogenic trypanosomes, infecting both humans and animals. In the present article, we dissected the possible role of members of the interleukin (IL)-12 family during infection with Trypanosoma brucei brucei and Trypanosoma evansi in mice. IL-12p35(-/-), IL-12p40(-/-), and IL-12p35(-/-)/p40(-/-) mice were susceptible to both pathogens, as was demonstrated by the increased mortality among these mice, compared with wild-type C57BL/6 mice. The different IL-12p70(-/-) mouse strains showed similar mortality kinetics, suggesting that IL-12p70--but not the IL-12p80 homodimer or IL-23--plays a crucial role in survival. Although there were similar plasma levels of immunoglobulin (Ig) M and IgG2a in IL-12-deficient mice and wild-type mice, interferon (IFN)- gamma production, especially during early infection, was severely impaired in all IL-12p70(-/-) mouse strains, demonstrating an IL-12p70-dependent mechanism for IFN- gamma production. Because IFN- gamma receptor-deficient mice (IFN- gamma R(-/-)) were also highly susceptible to both Trypanosoma species, IL-12p70-dependent IFN- gamma production seems to be the important mechanism involved in resistance against both pathogens.
authors.affiliation: Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. fbrombac@uctgsh1.uct.ac.za
authors.forename: Mark
authors.initials: M
authors.lastname: Barkhuizen
authors.forename: Stefan
authors.initials: S
authors.lastname: Magez
authors.forename: Robert A
authors.initials: RA
authors.lastname: Atkinson
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology*; D017471:Receptors, Interferon / Q000276:immunology; D016019:Survival Analysis; D014346:Trypanosoma brucei brucei / Q000276:immunology / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor