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Hamano, S. et al.

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production.

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-gamma 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-alpha, 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.[1]

References

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Hamano, S., Himeno, K., Miyazaki, Y., Ishii, K., Yamanaka, A., Takeda, A., Zhang, M., Hisaeda, H., Mak, T.W., Yoshimura, A., Yoshida, H. Immunity (2003) [Pubmed]

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