IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge

J Immunol. 2009 Jun 15;182(12):7353-63. doi: 10.4049/jimmunol.0900657.

Abstract

We examined the expression and influence of IL-10 during influenza infection. We found that IL-10 does not impact sublethal infection, heterosubtypic immunity, or the maintenance of long-lived influenza Ag depots. However, IL-10-deficient mice display dramatically increased survival compared with wild-type mice when challenged with lethal doses of virus, correlating with increased expression of several Th17-associated cytokines in the lungs of IL-10-deficient mice during the peak of infection, but not with unchecked inflammation or with increased cellular responses. Foxp3(-) CD4 T cell effectors at the site of infection represent the most abundant source of IL-10 in wild-type mice during high-dose influenza infection, and the majority of these cells coproduce IFN-gamma. Finally, compared with predominant Th1 responses in wild-type mice, virus-specific T cell responses in the absence of IL-10 display a strong Th17 component in addition to a strong Th1 response and we show that Th17-polarized CD4 T cell effectors can protect naive mice against an otherwise lethal influenza challenge and utilize unique mechanisms to do so. Our results show that IL-10 expression inhibits development of Th17 responses during influenza infection and that this is correlated with compromised protection during high-dose primary, but not secondary, challenge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Forkhead Transcription Factors / immunology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Interleukin-10 / deficiency*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Interleukin-17 / immunology*
  • Mice
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / metabolism
  • Survival Rate
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Antigens, Viral
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Interleukin-10