title: MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis.
abstract: Schistosomiasis is a chronic disease caused by the parasite of the Schistosoma genus and is characterized by egg-induced hepatic granulomas and fibrosis. Macrophages play a central role in schistosomiasis with several studies highlighting their differentiation into M2 cells involved in the survival of infected mice through limitation of immunopathology. However, little is known regarding the mechanisms of regulating macrophage differentiation. Here, we showed that the early stage of infection by Schistosoma japonicum induced expression of type 1T-helper-cell (Th1) cytokine, interferon-γ (IFN-γ), leading to increase in M1 cells. However, the presence of liver-trapped eggs induced the expression of Th2 cytokines including interleukin-4 (IL-4), IL-10, and IL-13 that upregulated the transcription of miR-146b by activating signal transducer and activator of transcription 3/6 (STAT3/6) that bind to the promoter of the pre-miR-146b gene. We found that the miR-146a/b was significantly upregulated in macrophages during the progression of hepatic schistosomiasis. The elevated miR-146a/b inhibited the IFN-γ-induced differentiation of macrophages to M1 cells through targeting STAT1. Our data indicate the protective roles of miR-146a/b in hepatic schistosomiasis through regulating the differentiation of macrophages into M2 cells.
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors: Xing
authors: X
authors: He
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China; Department of Pathogen Biology, Xuzhou Medical University, Xuzhou 221000, China.
authors: Rui
authors: R
authors: Tang
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China; Department of Pathogen Biology, Xuzhou Medical University, Xuzhou 221000, China.
authors: Yue
authors: Y
authors: Sun
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors: Yan-Ge
authors: YG
authors: Wang
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China.
authors: Kui-Yang
authors: KY
authors: Zhen
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China. Electronic address: dmzhangcn@163.com.
authors: Dong-Mei
authors: DM
authors: Zhang
authors: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai 200433, China. Electronic address: wqpan0912@aliyun.com.
authors: Wei-Qing
authors: WQ
authors: Pan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D008109:Liver Diseases, Parasitic / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D034622:RNA Interference; D050794:STAT1 Transcription Factor / Q000235:genetics*; D012552:Schistosomiasis / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D050794:STAT1 Transcription Factor
keywords: STAT pathway; hepatic schistosomiasis; macrophage differentiation; miR-146