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J Cell Mol Med. 2018 Jul;22(7):3353-3363. doi: 10.1111/jcmm.13610. Epub 2018 Mar 22.

IL-7 suppresses macrophage autophagy and promotes liver pathology in Schistosoma japonicum-infected mice.

Author information

1
Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
2
Department of Pathogen Biology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
3
Department of Anatomy, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.
4
Department of Pathology and Physiology, Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Jiangning District, Nanjing, Jiangsu, China.

Abstract

In schistosomiasis japonica and mansoni, parasite eggs trapped in host liver elicit severe liver granulomatous inflammation that subsequently leads to periportal fibrosis, portal hypertension, haemorrhage or even death. Macrophages are critical for granuloma formation and the development of liver fibrosis during schistosomiasis. However, whether the aberrant regulation of macrophage autophagy has an effect on the development of liver immunopathology in schistosomiasis remains to be elucidated. In this study, we showed that Schistosoma japonicum (S. japonicum) egg antigen (SEA)-triggered macrophage autophagy limited the development of pathology in host liver. However, engagement of IL-7 receptor (IL-7R/CD127) on macrophages by S. japonicum infection-induced IL-7 significantly suppressed SEA-triggered macrophage autophagy, which led to an enhanced liver pathology. In addition, anti-IL-7 neutralizing antibody or anti-CD127 blocking antibody treatment increased macrophage autophagy and suppressed liver pathology. Finally, we demonstrated that IL-7 protects macrophage against SEA-induced autophagy through activation of AMP-activated protein kinase (AMPK). Our study reveals a novel role for IL-7 in macrophage autophagy and identifies AMPK as a novel downstream mediator of IL-7-IL-7R signalling and suggests that manipulation of macrophage autophagy by targeting IL-7-IL-7R signalling may have the potential to lead to improved treatment options for liver pathogenesis in schistosomiasis.

KEYWORDS:

IL-7; Schistosomiasis; liver immunopathology; macrophage autophagy

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