Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.
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.
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Xiaojun
X
Chen
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Xiaowei
X
Yang
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Yong
Y
Li
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Jifeng
J
Zhu
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Sha
S
Zhou
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Zhipeng
Z
Xu
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.
Lei
L
He
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Xue
X
Xue
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Weiwei
W
Zhang
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Xiaoxiao
X
Dong
Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, United States of America.
Henry
H
Wu
Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America.
Carrie J
CJ
Li
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Hsiang-Ting
HT
Hsu
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Wenjun
W
Kong
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Feng
F
Liu
Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America.
Prem B
PB
Tripathi
Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America.
Michelle S
MS
Yu
Department of General Surgery, Kaiser LAMC, Los Angeles, California, United States of America.
Jason
J
Chang
Department of Pathology, Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Liang
L
Zhou
Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
Chuan
C
Su
D000818:Animals; D002478:Cells, Cultured; D006099:Granuloma / Q000276:immunology* / Q000469:parasitology; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012549:Schistosoma japonicum / Q000276:immunology / Q000472:pathogenicity*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000473:pathology; D012908:Snails / Q000469:parasitology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand