Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.
Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.
复制标题
小鼠 Cx3cr1 缺陷通过增强巨噬细胞的 M2 型极化来减轻急性血吸虫病期间肝肉芽肿的形成
DOI：
10.1242/dmm.018242
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发表时间：
2015-07-01
影响因子：
4.3
通讯作者：
Wang CY
中科院分区：
文献类型：
--
作者：
Ran L;Yu Q;Zhang S;Xiong F;Cheng J;Yang P;Xu JF;Nie H;Zhong Q;Yang X;Yang F;Gong Q;Kuczma M;Kraj P;Gu W;Ren BX;Wang CY
急性血吸虫病的特点是对组织或器官捕获的寄生虫虫卵的促炎反应以及肉芽肿的形成。在这里，我们描述了Cx3cr1 - / -小鼠的研究，并证明了Cx3cr1在急性血吸虫病期间肉芽肿形成的病理机制中的作用。缺乏Cx3cr1基因的小鼠可避免日本血吸虫虫卵引起的肉芽肿形成和肝损伤，表现为体重减轻，肝肿大减弱，肝功能保持不变。值得注意的是，日本血吸虫感染诱导肝脏Cx3cr1高水平表达，主要通过浸润性巨噬细胞表达。Cx3cr1的缺失使巨噬细胞优先倾向于M2极化，从而导致宿主免疫防御在急性血吸虫病期间从传统的Th1反应转变为典型的Th2反应。这种由Cx3cr1缺陷引起的免疫开关可能与STAT6/PPAR-γ信号的增强和吲哚胺2,3-双加氧酶（IDO）的表达增加有关，IDO是一种促进巨噬细胞M2极化的酶。综上所述，我们的数据提供了证据，表明CX3CR1可能是治疗急性血吸虫病的可行治疗靶点。在急性血吸虫病期间，CX3CR1信号的减少可以保护小鼠免受促炎反应和肝肉芽肿的形成。
Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1−/− mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis. Highlighted Article: A reduction in CX3CR1 signaling provides protection for mice against pro-inflammatory responses and hepatic granuloma formation during acute schistosomiasis.
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影响因子：
4.6
作者：
Sajic, Tatjana;Hainard, Alexandre;Scherl, Alexander;Wohlwend, Annelise;Negro, Francesco;Sanchez, Jean-Charles;Szanto, Ildiko
通讯作者：
Szanto, Ildiko
影响因子：
5.5
作者：
Dorgham, Karim;Ghadiri, Ata;Deterre, Philippe
通讯作者：
Deterre, Philippe
影响因子：
3.3
作者：
Mishra BB;Gundra UM;Teale JM
通讯作者：
Teale JM
影响因子：
4.4
作者：
Ishida, Yuko;Gao, Ji-Liang;Murphy, Philip M.
通讯作者：
Murphy, Philip M.
DOI：
10.1161/atvbaha.112.300930
发表时间：
2013-10-01
影响因子：
8.7
作者：
Poupel, Lucie;Boissonnas, Alexandre;Combadiere, Christophe
通讯作者：
Combadiere, Christophe