Interleukin-12p70 deficiency increases survival and diminishes pathology in Trypanosoma congolense infection.
To determine the immunological role played by interleukin (IL)-12 family members in Trypanosoma congolense infection, IL-12p35(-/-), IL-12p40(-/-), and IL-12p35(-/-)/p40(-/-) mice were used. While the latter 2 strains lack all IL-12 homologues, IL-12p35(-/-) mice still produce IL-12p80 homodimers and IL-23. Compared with wild-type mice, all infected IL-12-deficient mouse strains showed prolonged survival, whereas parasitemia levels were unaltered. Interferon (IFN)-gamma production in IL-12-deficient mice was strikingly reduced during the acute and chronic stages of infection, coinciding with significantly reduced chronic-stage hepatocellular damage, as demonstrated by histological analysis and plasma aspartate transaminase measurements. In contrast, IL-10 production was not affected by the absence of IL-12. Taken together, these results show that, during T. congolense infection, the absence of IL-12, but not the IL-12p80 homodimer or IL-23, leads to a reduction in IFN-gamma production, which reduces hepatic pathology and improves host survival in conjunction with IL-10 without negatively affecting parasitemia control.
Barkhuizen
Mark
M
Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Magez
Stefan
S
Ryffel
Bernhard
B
Brombacher
Frank
F
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics*; D053759:Interleukin-23 / Q000235:genetics; D008099:Liver / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology; D021122:Protein Subunits; D013997:Time Factors; D014348:Trypanosoma congolense; D014353:Trypanosomiasis, African / Q000235:genetics* / Q000276:immunology* / Q000473:pathology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D053759:Interleukin-23; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma