Parasites & Vectors, 14 June 2019, DOI:https://doi.org/10.1186/s13071-019-3542-4

Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression

Zhi-Yong Li, LinZhuo Xiao, GuiYing Lin, JuanJuan Tang, YuQiang Chen, Lan Chen, BaoQi Li, MeiLing Wu, ShuYan Liu, ChuQin Huang, Dominique Ferrandon & Zi Li

1 Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, 511436, Guangdong Province, People’s Republic of China

2 RIDI UPR9022 du CNRS, Université de Strasbourg, 67000, Strasbourg, France

Abstract

Background

Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established.

Results

This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection.

Conclusions

These results indicate that during Sj infection tTG may control liver fibrosis at least partially through TLR4, NF-κB pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj infection.

文章链接：https://link.springer.com/article/10.1186/s13071-019-3542-4#citeas