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

Shinjiro Hamano, Kunisuke Himeno, Yoshiyuki Miyazaki, Kazunari Ishii, Atsushi Yamanaka, Atsunobu Takeda, Manxin Zhang, Hajime Hisaeda, Tak W. Mak, Akihiko Yoshimura, Hiroki Yoshida

Research output: Contribution to journalArticle

213 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)657-667
Number of pages11
JournalImmunity
Volume19
Issue number5
DOIs
Publication statusPublished - 2003 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Hamano, S., Himeno, K., Miyazaki, Y., Ishii, K., Yamanaka, A., Takeda, A., Zhang, M., Hisaeda, H., Mak, T. W., Yoshimura, A., & Yoshida, H. (2003). WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity, 19(5), 657-667. https://doi.org/10.1016/S1074-7613(03)00298-X