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IL-22-induced cell extrusion and IL-18-induced cell death prevent and cure rotavirus infection

Abstract : 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 cyto-kines 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.
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Submitted on : Tuesday, October 13, 2020 - 8:26:34 AM
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Zhan Zhang, Jun Zou, Zhenda Shi, Benyue Zhang, Lucie Etienne-Mesmin, et al.. IL-22-induced cell extrusion and IL-18-induced cell death prevent and cure rotavirus infection. Science Immunology, American Association for the Advancement of Science, 2020, 5 (52), pp.eabd2876. ⟨10.1126/sciimmunol.abd2876⟩. ⟨hal-02965130⟩



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