WSX-1 Is Required for Resistance to Trypanosoma cruzi Infection by Regulation of Proinflammatory Cytokine Production

Abstract WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi . WSX-1 −/− mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1 −/− splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1 −/− mice, and IFN-γ that was overproduced in WSX-1 −/− mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-α, were produced by liver mononuclear cells in WSX-1 −/− mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.