首页> 外文期刊>American Journal of Physiology >IL-4R{alpha}-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis.
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IL-4R{alpha}-responsive smooth muscle cells increase intestinal hypercontractility and contribute to resistance during acute Schistosomiasis.

机译:在急性血吸虫病期间,IL-4R {α}反应性平滑肌细胞可增加肠道过度收缩性并有助于抵抗。

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摘要

Interleukin-(IL)-4 and IL-13 signal through heterodimeric receptors containing a common IL-4 receptor-alpha (IL-4Ralpha) subunit, which is important for protection against helminth infections, including schistosomiasis. Previous studies demonstrated important roles for IL-4Ralpha-responsive hematopoietic cells, including T cells and macrophages in schistosomiasis. In this study, we examined the role of IL-4Ralpha responsiveness by nonhematopoietic smooth muscle cells during experimental acute murine schistosomiasis. Comparative Schistosoma mansoni infection studies with smooth muscle cell-specific IL-4Ralpha-deficient (SM-MHC(cre)IL-4Ralpha(-/flox)) mice, heterozygous control (IL-4Ralpha(-/flox)) mice, and global IL-4Ralpha-deficient (IL-4Ralpha(-/-)) mice were conducted. S. mansoni-infected SM-MHC(cre)IL-4Ralpha(-/flox) mice showed increased weight loss and earlier mortalities compared with IL-4Ralpha(-/flox) mice, despite comparable T(H)2/type 2 immune responses. In contrast to highly susceptible IL-4Ralpha-deficient mice, increased susceptibility in SM-MHC(cre)IL-4Ralpha(-/flox) mice was not accompanied by intestinal tissue damage and subsequent sepsis. However, both susceptible mutant mouse strains failed to efficiently expel eggs, demonstrated by egg reduction in the feces compared with control mice. Reduced egg expulsion was accompanied by impaired IL-4/IL-13-mediated hypercontractile intestinal responses, which was present in the more resistant control mice. Together, we conclude that IL-4Ralpha responsiveness by smooth muscle cells and subsequent IL-4- and IL-13-mediated hypercontractility are required for host protection during acute schistosomiasis to efficiently expel S. mansoni eggs and to prevent premature mortality.
机译:白介素-(IL)-4和IL-13通过含有共同的IL-4受体-α(IL-4Ralpha)亚基的异二聚体受体发出信号,这对于预防包括血吸虫病在内的蠕虫感染很重要。先前的研究证明了血吸虫病中IL-4Ralpha反应性造血细胞(包括T细胞和巨噬细胞)的重要作用。在这项研究中,我们检查了实验性急性鼠血吸虫病中非造血平滑肌细胞对IL-4Ralpha应答的作用。比较曼氏血吸虫感染研究的平滑肌细胞特异性IL-4Ralpha缺陷(SM-MHC(cre)IL-4Ralpha(-/ flox))小鼠,杂合对照(IL-4Ralpha(-/ flox))小鼠和全球进行IL-4Ralpha缺陷(IL-4Ralpha(-/-))小鼠。与IL-4Ralpha(-/ flox)小鼠相比,曼氏沙门氏菌感染的SM-MHC(cre)IL-4Ralpha(-/ flox)小鼠显示出增加的体重减轻和更短的死亡率,尽管具有类似的T(H)2/2型免疫回应。与高度敏感的IL-4Ralpha缺陷小鼠相反,SM-MHC(cre)IL-4Ralpha(-/ flox)小鼠的易感性增加并未伴随肠组织损伤和随后的败血症。但是,这两种易感突变小鼠品系均未能有效排出卵,这是通过与对照小鼠相比粪便中卵减少所证实的。减少的卵排出伴随着IL-4 / IL-13介导的过度收缩性肠反应的减弱,这在抵抗力更强的对照小鼠中存在。在一起,我们得出结论,急性血吸虫病期间,寄主保护需要平滑肌细胞的IL-4Ralpha反应性以及随后的IL-4-和IL-13介导的过度收缩,才能有效地排出曼氏沙门氏菌卵并防止过早死亡。

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