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 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.
Bai
Fengwei
F
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Town
Terrence
T
Qian
Feng
F
Wang
Penghua
P
Kamanaka
Masahito
M
Connolly
Tarah M
TM
Gate
David
D
Montgomery
Ruth R
RR
Flavell
Richard A
RA
Fikrig
Erol
E
D000818:Animals; D009033:Culicidae / Q000821:virology; D016207:Cytokines / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D017741:Survivors; D014765:Viral Vaccines; D014901:West Nile Fever / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D014902:West Nile virus / Q000472:pathogenicity*
D016207:Cytokines; D014765:Viral Vaccines; D016753:Interleukin-10