Follicular Helper T Cells Promote Liver Pathology in Mice during Schistosoma japonicum Infection

PLoS Pathogens

Liang Zhou¹  Xiaojun Chen²  Weiwei Zhang²  Lei He²  Xiaoxiao Dong²  Feng Liu²  Wenjun Kong²  Sha Zhou²  Jifeng Zhu²  Prem B. Tripathi²  Henry Wu²  Xiaowei Yang²  Yong Li²  Zhipeng Xu²  Chuan Su³  Xue Xue³  Carrie J. Li⁴  Jason Chang⁵  Hsiang-Ting Hsu⁵  Michelle S. Yu⁵ 

[1] Department of General Surgery, Kaiser LAMC, Los Angeles, California, United States of America;Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China;Department of Pathology, Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America;Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, United States of America;Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America

关键词: Macrophages;    T cells;    Schistosoma japonicum;    Granulomas;    Spleen;    B cells;    Lymph nodes;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1004097

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell–cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40–CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

【 授权许可】

CC BY