Interleukin-12p70 Deficiency Increases Survival and Diminishes Pathology in Trypanosoma congolense Infection

Barkhuizen, Mark; Magez, Stefan; Ryffel, Bernhard; Brombacher, Frank
November 2008
Journal of Infectious Diseases;11/1/2008, Vol. 198 Issue 9, p1284
Academic Journal
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)-γ 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-γ production, which reduces hepatic pathology and improves host survival in conjunction with IL-10 without negatively affecting parasitemia control.


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