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

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26 Citations (Scopus)


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.

Original languageEnglish
Article numbere0005614
JournalPLoS Neglected Tropical Diseases
Issue number5
Publication statusPublished - 2017 May 24

Bibliographical note

Publisher Copyright:
© 2017 Kim et al.

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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