Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages

Disease Models & Mechanisms

Hao Nie¹  Fei Yang¹  Jun-Fa Xu²  Quan Gong³  Lin Ran⁴  Xueli Yang⁴  Bo-Xu Ren⁴  Cong-Yi Wang⁴  Qin Zhong⁴  Weikuan Gu⁵  Jia Cheng⁶  Shu Zhang⁶  Qilin Yu⁶  Ping Yang⁶  Fei Xiong⁶  Piotr Kraj⁷  Michal Kuczma⁷ 

[1] Clinical and Molecular Immunology Research Center, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China,;Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College, No. 1 Xincheng Road, Dongguan 523808, China;Department of Immunology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China;Department of Molecular Biology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China;Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee, Health Science Center, Memphis, TN 38163, USA;The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China;The Center for Biotechnology and Genomic Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA;

关键词: CX3CR1;    Schistosomiasis;    Granuloma formation;    Macrophage;    STAT-6;    PPAR-γ;   

DOI  :  10.1242/dmm.018242

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown