IL-10 Signaling Blockade Controls Murine West Nile Virus Infection: e1000610

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 pathoge...

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Bibliographic Details
Published in:PLoS pathogens 2009-10, Vol.5 (10)
Main Authors: Bai, Fengwei, Town, Terrence, Qian, Feng, Wang, Penghua, Kamanaka, Masahito, Connolly, Tarah M, Gate, David, Montgomery, Ruth R, Flavell, Richard A, Fikrig, Erol
Format: Article
Language:English
Subjects:
Immune system
Infections
Vector-borne diseases
Viral infections
West Nile virus
Online Access:Get full text
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Summary: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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1000610