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:10.1371/journal.ppat.1000610

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

Abstract

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, andmay be an important cellular source of IL-10 duringWNV 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.

Original language	English (US)
Article number	e1000610
Journal	PLoS pathogens
Volume	5
Issue number	10
DOIs	https://doi.org/10.1371/journal.ppat.1000610
State	Published - Oct 2009
Externally published	Yes

ASJC Scopus subject areas

Genetics
Molecular Biology
Virology
Parasitology
Microbiology
Immunology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.ppat.1000610

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@article{57aed34b3df246768c1eebf7c38b689f,

title = "IL-10 signaling blockade controls murine West Nile virus infection",

abstract = "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, andmay be an important cellular source of IL-10 duringWNV 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.",

author = "Fengwei Bai and Terrence Town and Feng Qian and Penghua Wang and Masahito Kamanaka and Connolly, {Tarah M.} and David Gate and Montgomery, {Ruth R.} and Flavell, {Richard A.} and Erol Fikrig",

year = "2009",

month = oct,

doi = "10.1371/journal.ppat.1000610",

language = "English (US)",

volume = "5",

journal = "PLoS pathogens",

issn = "1553-7366",

publisher = "Public Library of Science",

number = "10",

}

TY - JOUR

T1 - IL-10 signaling blockade controls murine West Nile virus infection

AU - Bai, Fengwei

AU - Town, Terrence

AU - Qian, Feng

AU - Wang, Penghua

AU - Kamanaka, Masahito

AU - Connolly, Tarah M.

AU - Gate, David

AU - Montgomery, Ruth R.

AU - Flavell, Richard A.

AU - Fikrig, Erol

PY - 2009/10

Y1 - 2009/10

N2 - 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, andmay be an important cellular source of IL-10 duringWNV 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.

AB - 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, andmay be an important cellular source of IL-10 duringWNV 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.

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DO - 10.1371/journal.ppat.1000610

M3 - Article

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SN - 1553-7366

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JO - PLoS pathogens

JF - PLoS pathogens

IS - 10

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ER -

IL-10 signaling blockade controls murine West Nile virus infection

Abstract

ASJC Scopus subject areas

UN SDGs

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