IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections
IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections
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DOI：
10.1038/mi.2010.46
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发表时间：
2011-01-01
影响因子：
8
通讯作者：
Brombacher, F.
中科院分区：
文献类型：
--
作者：
Horsnell, W. G. C.;Vira, A.;Brombacher, F.
巴西拟青霉感染可引起肺部病变，这种病变可能与宿主免疫反应的T(H)2极化有关。我们提供的数据表明，巴西奈瑟氏菌驱动的呼吸道粘液产生依赖于平滑肌细胞白介素4受体-α(IL-4Rα)的反应性。在感染后第7天和第10天，IL-4Rα(-/lox)对照组小鼠有显著的呼吸道粘液产生，而全局敲除(IL-4Rα(-/-))和平滑肌特异性IL-4Rα缺陷小鼠(SM-MHCCre IL-4Rα(-/lox))则显示呼吸道粘液反应减弱。此外，SM-MHCCre IL-4Rα(-/lox)小鼠的IL-13和IL-5细胞因子的产生受到损害，并伴随着肺中T细胞数量的一过性减少。分泌的巴西奈瑟氏原虫排泄分泌抗原(NES)体外处理血管平滑肌细胞可诱导IL-6的产生。在NES刺激的细胞中，依赖蛋白激酶C(PKC)的平滑肌细胞增殖减少，并伴随着细胞周期停滞。综上所述，这些数据表明，IL-4Rα和NES驱动的平滑肌细胞反应在启动T(H)2对巴西奈瑟氏菌感染的反应中做出了重要贡献。
Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T(H)2 polarization of the host's immune response. We present data demonstrating N. brasiliensis-driven airway mucus production to be dependent on smooth muscle cell interleukin 4 receptor-alpha (IL-4R alpha) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4R alpha(-/lox) control mice, whereas global knockout (IL-4R alpha(-/-)) and smooth muscle-specific IL-4R alpha-deficient mice (SM-MHCCre IL-4R alpha(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHCCre IL-4R alpha(-/lox) mice was impaired along with a transient reduction in T-cell numbers in the lung. In vitro treatment of smooth muscle cells with secreted N. brasiliensis excretory -secretory antigen (NES) induced IL-6 production. Decreased protein kinase C (PKC)-dependent smooth muscle cell proliferation associated with cell cycle arrest was found in cells stimulated with NES. Together, these data demonstrate that both IL-4R alpha and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections.