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

Immunity. 2003 Nov;19(5):657-67. doi: 10.1016/s1074-7613(03)00298-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood / microbiology
  • Chagas Disease / immunology*
  • Chagas Disease / metabolism
  • Chagas Disease / mortality
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Liver / pathology
  • Mice
  • Mice, Knockout
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin
  • Spleen / metabolism
  • Th2 Cells / metabolism
  • Trypanosoma cruzi


  • Cytokines
  • Il27ra protein, mouse
  • Receptors, Cytokine
  • Receptors, Interleukin