Trypanosoma cruzi is a potent inducer of interleukin-12 production in macrophages

Abstract

Cytokines produced after infection with Trypanosoma cruzi have been shown to be crucial in the de-termination of resistance or susceptibility. Interferon-γ (IFN-γ) is the predominant cytokine produced after infection and has been shown to protect susceptible mice from infection. IFN-γ production by natural killer cells and T cells is induced by interleukin-12 (IL-12). Therefore, the aim of our study was to analyze the ability of T. cruzi to induce IL-12 production. Spleen cells and bone marrow-derived macrophages incubated with T. cruzi trypomastigotes induced high amounts of IL-12p40 mRNA as shown by reverse transcriptase-polymerase chain reaction. Lipopolysaccharide (LPS) was less efficient in inducing IL-12p40-specific mRNA. Furthermore, biologically active IL-12, detected by the capacity of the supernatant of infected macrophages to induce IFN-γ production in spleen cells, was produced at very high levels. In comparison, macrophages stimulated with LPS secreted drastically less IL-12. Interestingly, only live, UV- or gamma-irradiated trypanosomes, but not heat-killed parasites or lysates, were functional in this respect. In a kinetic study, in the supernatant obtained from cultures of infected macrophages, IL-12 was already detectable at 2 h after infection, peaked at 32 h and declined after 45 h.