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

研究成果: ジャーナルへの寄稿学術誌査読

227 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)657-667
ページ数11
ジャーナルImmunity
19
5
DOI
出版ステータス出版済み - 11月 2003

!!!All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学
  • 感染症

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