Open AccessIL-10 Signaling Blockade Controls Murine West Nile Virus Infection
Author(s) -
Fengwei Bai,
Terrence Town,
Feng Qian,
Penghua Wang,
Masahito Kamanaka,
Tarah M. Connolly,
David Gate,
Ruth R. Montgomery,
Richard A. Flavell,
Erol Fikrig
Publication year - 2009
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1000610
Subject(s) - flavivirus , virology , blockade , biology , in vivo , immunology , pathogenesis , virus , vero cell , immunity , immune system , receptor , biochemistry , microbiology and biotechnology
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.