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Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo

 Eun-Min Kim  ;  You Shine Kwak  ;  Myung-Hee YI  ;  Ju Yeong Kim  ;  Woon-Mok Sohn  ;  Tai-Soon Yong 
 PLOS NEGLECTED TROPICAL DISEASES, Vol.11(5) : e0005614, 2017 
Journal Title
Issue Date
Animals ; Antigens, Helminth/immunology* ; Cell Differentiation ; Clonorchis sinensis/immunology* ; Liver/parasitology* ; Liver/pathology* ; Macrophage Activation ; Macrophages/immunology* ; Male ; Mice, Inbred BALB C
Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs) resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages) and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages). Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype), which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection.
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1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Min(김은민)
Kim, Ju Young(김주영) ORCID logo https://orcid.org/0000-0003-2456-6298
Yong, Tai Soon(용태순) ORCID logo https://orcid.org/0000-0002-3445-0769
Yi, Myung Hee(이명희) ORCID logo https://orcid.org/0000-0001-9537-5726
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