title: Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ran
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College, No. 1 Xincheng Road, Dongguan 523808, China.
authors.forename: Jun-Fa
authors.initials: JF
authors.lastname: Xu
authors.affiliation: Clinical and Molecular Immunology Research Center, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Molecular Biology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Department of Molecular Biology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Clinical and Molecular Immunology Research Center, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Immunology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Gong
authors.affiliation: The Center for Biotechnology and Genomic Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Kuczma
authors.affiliation: The Center for Biotechnology and Genomic Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kraj
authors.affiliation: Department of Orthopedic Surgery and BME, Campbell-Clinic, University of Tennessee, Health Science Center, Memphis, TN 38163, USA.
authors.forename: Weikuan
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Molecular Biology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China boxuren188@163.com wangcy@tjh.tjmu.edu.cn.
authors.forename: Bo-Xu
authors.initials: BX
authors.lastname: Ren
authors.affiliation: Department of Molecular Biology, Medical College of Yangtze University, 1 Nanhuan Road, Jingzhou, Hubei 434023, China The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College, No. 1 Xincheng Road, Dongguan 523808, China boxuren188@163.com wangcy@tjh.tjmu.edu.cn.
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010063:Ovum / Q000276:immunology; D047495:PPAR gamma / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000172:deficiency* / Q000235:genetics; D050800:STAT6 Transcription Factor / Q000378:metabolism; D012549:Schistosoma japonicum / Q000276:immunology; D012554:Schistosomiasis japonica / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D047495:PPAR gamma; D023062:Receptors, Interleukin-8A; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse
keywords: CX3CR1; Granuloma formation; Macrophage; PPAR-γ; STAT-6; Schistosomiasis