1. IL-22–induced cell extrusion and IL-18–induced cell death prevent and cure rotavirus infection
- Author
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Benyue Zhang, Andrew T. Gewirtz, Zhan Zhang, Yanling Wang, Jun Zou, Zhenda Shi, Lucie Etienne-Mesmin, Xuyan Shi, Feng Shao, Benoit Chassaing, Center for Inflammation, Immunity & Infection [Atlanta, GA, États-Unis], Institute for Biomedical Sciences [Atlanta, GA, États-Unis], Georgia State University [Atlanta, GA, États-Unis]-Georgia State University [Atlanta, GA, États-Unis], Microbiologie Environnement Digestif Santé (MEDIS), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Institute of Biological Sciences [Beijing, China] (Number 7 Science Park Road), Zhongguancun Life Science Park [Beijing, China], Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Paris, France, Neuroscience Institute, Georgia State University, Atlanta, Etats-Unis, Georgia State University, University System of Georgia (USG)-University System of Georgia (USG), and United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USADK083890DK099071American Diabetes Association European Research Council (ERC)Kenneth Rainin Foundation Paris University
- Subjects
Male ,Rotavirus ,0301 basic medicine ,Programmed cell death ,Immunology ,Cell ,Biology ,medicine.disease_cause ,Rotavirus Infections ,Article ,Virus ,Microbiology ,Interleukin 22 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Movement ,medicine ,Animals ,Humans ,Intestinal Mucosa ,Receptor ,Cell Proliferation ,Mice, Knockout ,Interleukins ,Interleukin-18 ,Epithelial Cells ,General Medicine ,Anoikis ,3. Good health ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,cellule épithéliale intestinale ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Interleukin 18 ,030217 neurology & neurosurgery ,Signal Transduction - 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.
- Published
- 2020