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

被引：239

作者：

Hamano, S

Himeno, K

Miyazaki, Y

Ishii, K

Yamanaka, A

Takeda, A

Zhang, M

Hisaeda, H

Mak, TW

Yoshimura, A

Yoshida, H ^{[1
]}

机构：

[1] Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Fukuoka 8128582, Japan

[2] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada

[3] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada

[4] Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada

[5] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3330012, Japan

[6] Kyushu Univ, Fac Med Sci, Dept Parasitol, Fukuoka 8128582, Japan

来源：

IMMUNITY | 2003年 / 19卷 / 05期

关键词：

D O I：

10.1016/S1074-7613(03)00298-X

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：657 / 667

页数：11

共 40 条

[21] EFFECT OF ANTI-GAMMA-INTERFERON AND ANTI-INTERLEUKIN-4 ADMINISTRATION ON THE RESISTANCE OF MICE AGAINST INFECTION WITH RETICULOTROPIC AND MYOTROPIC STRAINS OF TRYPANOSOMA-CRUZI [J].