PLoS Pathogens (Oct 2009)

IL-10 signaling blockade controls murine West Nile virus infection.

  • Fengwei Bai,
  • Terrence Town,
  • Feng Qian,
  • Penghua Wang,
  • Masahito Kamanaka,
  • Tarah M Connolly,
  • David Gate,
  • Ruth R Montgomery,
  • Richard A Flavell,
  • Erol Fikrig

DOI
https://doi.org/10.1371/journal.ppat.1000610
Journal volume & issue
Vol. 5, no. 10
p. e1000610

Abstract

Read online

West Nile virus (WNV), a mosquito-borne single-stranded RNA flavivirus, can cause significant human morbidity and mortality. Our data show that interleukin-10 (IL-10) is dramatically elevated both in vitro and in vivo following WNV infection. Consistent with an etiologic role of IL-10 in WNV pathogenesis, we find that WNV infection is markedly diminished in IL-10 deficient (IL-10(-/-)) mice, and pharmacologic blockade of IL-10 signaling by IL-10 neutralizing antibody increases survival of WNV-infected mice. Increased production of antiviral cytokines in IL-10(-/-) mice is associated with more efficient control of WNV infection. Moreover, CD4(+) T cells produce copious amounts of IL-10, and may be an important cellular source of IL-10 during WNV infection in vivo. In conclusion, IL-10 signaling plays a negative role in immunity against WNV infection, and blockade of IL-10 signaling by genetic or pharmacologic means helps to control viral infection, suggesting a novel anti-WNV therapeutic strategy.