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IL-10 Signaling Blockade Controls Murine West Nile Virus Infection

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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Detalles Bibliográficos
Autores principales: Bai, Fengwei, Town, Terrence, Qian, Feng, Wang, Penghua, Kamanaka, Masahito, Connolly, Tarah M., Gate, David, Montgomery, Ruth R., Flavell, Richard A., Fikrig, Erol
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749443/
https://www.ncbi.nlm.nih.gov/pubmed/19816558
http://dx.doi.org/10.1371/journal.ppat.1000610
Descripción
Sumario: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.