Enhancement of natural killer (NK) cell cytotoxicity and induction of NK cell-derived interferon-gamma (IFN-gamma) display different kinetics during experimental infection with Trypanosoma cruzi

Early immunological activation involves an initial phase of cytokine activity and involvement of cell types such as NK cells. Such early immune responses are often decisive in resolution of microbial infection. NK cells reduce parasitaemia and enhance survival in experimental Trypanosoma cruzi infection, although the nature of these protective effects is not well understood. In this study, a detailed analysis of innate cytokine induction in the absence and presence of NK cells during the first 8 days of infection was performed. Following intraperitoneal infection with a high dose of parasites, reverse transcriptase-polymerase chain reaction showed that splenic mRNA for IFN-gamma appeared as a peak 24 h after infection and then reappeared 2-3 days later. In NK-depleted animals the first peak of IFN-gamma was absent and the second wave was slightly delayed. mRNA for IL-12 and tumour necrosis factor-alpha (TNF-alpha) as well as IFN-alpha protein in serum was only recorded 24 h after infection, at the same time as the IFN-gamma peak. NK depletion resulted in a small decrease of IL-12 mRNA levels, whereas TNF-alpha and IFN-alpha were not affected. NK cytotoxicity remained elevated throughout the 8 days and thus did not parallel the expression of IFN-gamma production by NK cells. We conclude that NK cell cytokine production and cytolytic activity play different roles in response to challenge with T. cruzi.