Role of IFN‐α/β and IL‐12 in the activation of natural killer cells and interferon‐γ production during experimental infection with Trypanosoma cruzi
Control of Trypanosoma cruzi infection depends largely upon the production of interferon (IFN)‐γ. During experimental infection this cytokine is produced early, mainly by natural killer (NK) cells and later by T cells. As NK cells have been reported to participate in defence against T. cruzi, it is of importance to study the regulation of NK cell functions during infection with the parasite. Several innate cytokines regulate NK cell activity, among them being interferon (IFN)‐α and IFN‐β (type 1 IFNs) and interleukin (IL)‐12, which have all been reported to be involved in protection against T. cruzi. The role of these cytokines in regulation of NK cell functions and disease outcome were studied by infection of mutant mice lacking the IFN‐α/β receptor (IFNα/βR–/–) or IL‐12 (IL‐12–/–) with T. cruzi. IFNα/βR–/– mice were unable to activate the cytotoxic response but produced IFN‐γ, and were not more susceptible than controls. IL‐12–/– mice were extremely susceptible and failed to produce T cell‐derived IFN‐γ and nitric oxide (NO), although NK cytotoxicity was induced. The results indicate that IL‐12 protects against T. cruzi by initiating T cell‐mediated production of IFN‐γ, but that endogenous IFN‐α/β and NK cell cytotoxicity are not of major importance in defence.