Interleukin-12p70-dependent interferon- gamma production is crucial for resistance in African trypanosomiasis.
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.
Barkhuizen
Mark
M
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
Magez
Stefan
S
Atkinson
Robert A
RA
Brombacher
Frank
F
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
D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor