WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production
WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production
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DOI：
10.1016/s1074-7613(03)00298-x
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发表时间：
2003-11-01
期刊：
影响因子：
32.4
通讯作者：
Yoshida, H
中科院分区：
文献类型：
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作者：
Hamano, S;Himeno, K;Yoshida, H
WSX-1是一种I类细胞因子受体，与IL-12受体具有同源性，并且对于抵抗主要利什曼原虫感染是必需的。在本研究中，我们证明了WSX-1也是抵抗克氏锥虫所必需的。与野生型小鼠相比，WSX-1（-/-）小鼠表现出长期寄生虫血症、严重肝损伤和死亡率增加。WSX-1（-/-）脾细胞产生的Th 2细胞因子水平升高，这是造成寄生虫血症延长的原因。在受感染的WSX-1（-/-）小鼠的肝脏中观察到大量的坏死性炎性病变，与野生型小鼠相比，WSX-1（-/-）小鼠中过量产生的IFN-γ是造成病变的原因。此外，WSX-1（-/-）小鼠肝脏单核细胞产生大量的各种促炎细胞因子，包括IL-6和TNF-α。因此，在T.在克氏感染中，WSX-1通过调节促炎细胞因子的产生来抑制肝损伤，同时通过抑制Th 2应答来控制寄生虫血症，证明了其作为细胞因子产生的抑制性调节剂的新作用。
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.