| First Author | Zhang Z | Year | 2020 |
| Journal | Sci Immunol | Volume | 5 |
| Issue | 52 | PubMed ID | 33008915 |
| Mgi Jnum | J:297124 | Mgi Id | MGI:6471966 |
| Doi | 10.1126/sciimmunol.abd2876 | Citation | Zhang Z, et al. (2020) IL-22-induced cell extrusion and IL-18-induced cell death prevent and cure rotavirus infection. Sci Immunol 5(52) |
| abstractText | 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. |
