Open AccessIL-22–induced cell extrusion and IL-18–induced cell death prevent and cure rotavirus infection
Author(s) -
Zhan Zhang,
Jun Zou,
Zhenda Shi,
Benyue Zhang,
Lucie EtienneMesmin,
Yanling Wang,
Xuyan Shi,
Feng Shao,
Benoît Chassaing,
Andrew T. Gewirtz
Publication year - 2020
Publication title -
science immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.83
H-Index - 51
ISSN - 2470-9468
DOI - 10.1126/sciimmunol.abd2876
Subject(s) - rotavirus , cell , programmed cell death , extrusion , virology , cell formation , immunology , biology , medicine , microbiology and biotechnology , virus , apoptosis , biochemistry , genetics , materials science , metallurgy , mathematical optimization , mathematics
Bacterial flagellin can elicit production of TLR5-mediated IL-22 and NLRC4-mediated IL-18 cytokines that act in concert to cure and prevent rotavirus (RV) infection. This study investigated the mechanism by which these cytokines act to impede RV. Although IL-18 and IL-22 induce each other's expression, we found that IL-18 and IL-22 both impeded RV independently of one another and did so by distinct mechanisms that involved activation of their cognate receptors in intestinal epithelial cells (IEC). IL-22 drove IEC proliferation and migration toward villus tips, which resulted in increased extrusion of highly differentiated IEC that serve as the site of RV replication. In contrast, IL-18 induced cell death of RV-infected IEC thus directly interrupting the RV replication cycle, resulting in spewing of incompetent virus into the intestinal lumen and causing a rapid drop in the number of RV-infected IEC. Together, these actions resulted in rapid and complete expulsion of RV, even in hosts with severely compromised immune systems. These results suggest that a cocktail of IL-18 and IL-22 might be a means of treating viral infections that preferentially target short-lived epithelial cells.