IL-10 Signaling Blockade Controls Murine West Nile Virus Infection

PLoS Pathogens

Feng Qian¹  Ruth R. Montgomery¹  Masahito Kamanaka²  Erol Fikrig²  Penghua Wang³  Terrence Town⁴  Fengwei Bai⁵  David Gate⁵  Tarah M. Connolly⁶  Richard A. Flavell⁶ 

[1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America;Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America;Departments of Neurosurgery and Biomedical Sciences, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America;L2 Diagnostics, LLC, New Haven, Connecticut, United States of America;Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America;Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America

关键词: West Nile virus;    T cells;    Mouse models;    Macrophages;    Cytokines;    Enzyme-linked immunoassays;    Immune response;    Antibodies;   

DOI  :  10.1371/journal.ppat.1000610

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY