About this item:

646 Views | 789 Downloads

Author Notes:

Corresponding Author: A.T. Gewirtz, E-mail: agewirtz@gsu.edu

We thank H. Virgin, T. Nice, A.-U. Rasheed, R. Ahmed, G. Silvestri, B. Rouse, B. Pulendran, A. Lukacher, S-M. Kang, and D. Kalman for helpful discussions. We thank D. Moore and K. Yu for technical support.

Recombinant IL-22, antibodies to IL-17 and IL-22, and Il22−/− mice were provided under a materials transfer agreement by Genentech (South San Francisco, CA).

Patents for use of flagellin and IL-22/IL-18 to treat or prevent viral infection have been applied for under application nos. PCT/US2011/052301 (Emory University) and 61/888/439 (Georgia State University, provisional).

RNA-sequencing data are deposited in Gene Expression Omnibus with accession no. GSE62479.

Subjects:

Research Funding:

This work was supported by NIH grants DK061417—and an accompanying award from the American Reinvestment and Recovery Act—AI107943, DK064730, DK56338, AI038296, and AI080656.

B.C. is supported by a fellowship from the Crohn’s and Colitis Foundation of America.

T.S.D. is supported by Elizabeth B. Lamb Center for Pediatric Research.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • CD8(+) T-CELLS
  • DENDRITIC CELLS
  • BACTERIAL FLAGELLIN
  • NLRC4
  • SALMONELLA
  • PROTECTS
  • DIARRHEA
  • IMMUNITY
  • MUCOSAL
  • DEFENSE

Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18

Show all authors Show less authors

Tools:

Journal Title:

Science

Volume:

Volume 346, Number 6211

Publisher:

, Pages 861-865

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Activators of innate immunity may have the potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin-22 (IL-22), which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection and thus holds promise as a broad-spectrum antiviral agent.

Copyright information:

© 2014 by the American Association for the Advancement of Science; all rights reserved.

Export to EndNote