Prevention and cure of rotavirus infection via TLR5/NLRC4–mediated production of IL-22 and IL-18 Article (Web of Science)

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.

authors

  • Zhang, Benyue
  • Chassaing, Benoit
  • Shi, Zhenda
  • Uchiyama, Robin
  • Zhang, Zhan
  • Denning, Timothy L.
  • Crawford, Sue E.
  • Pruijssers, Andrea J.
  • Iskarpatyoti, Jason A.
  • Estes, Mary K.
  • Dermody, Terence S.
  • Ouyang, Wenjun
  • Williams, Ifor R.
  • Kumar, Matam Vijay
  • Gewirtz, Andrew T.

publication date

  • 2014

webpage

published in

number of pages

  • 4

start page

  • 861

end page

  • 865

volume

  • 346

issue

  • 6211