A paradoxical role for neutrophils in the pathogenesis of West Nile virus.
Polymorphonuclear leukocytes (PMNs) are key in innate immunity, but their role in viral pathogenesis is incompletely understood. In infection due to West Nile virus (WNV), we found that expression of 2 PMN-attracting chemokines, Cxcl1 and Cxcl2, was rapidly and dramatically elevated in macrophages. PMNs are rapidly recruited to the site of WNV infection in mice and support efficient replication of WNV. Mice depleted of PMNs after WNV inoculation developed higher viremia and experienced earlier death, compared with the control group, which suggest a protective role for PMNs. In contrast, when PMNs were depleted prior to infection with WNV, and in mice deficient in Cxcr2 (a chemokine receptor gene), viremia was reduced and survival was enhanced. Collectively, these data suggest that PMNs have a biphasic response to WNV infection, serving as a reservoir for replication and dissemination in early infection and later contributing to viral clearance.
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520‐8031, USA.
Fengwei
F
Bai
Kok-Fai
KF
Kong
Jianfeng
J
Dai
Feng
F
Qian
Lin
L
Zhang
Charles R
CR
Brown
Erol
E
Fikrig
Ruth R
RR
Montgomery
D000818:Animals; D054360:Chemokine CXCL1 / Q000276:immunology; D054426:Chemokine CXCL2 / Q000172:deficiency / Q000276:immunology; D005260:Female; D047589:Leukocyte Reduction Procedures; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000276:immunology* / Q000821:virology*; D016019:Survival Analysis; D013997:Time Factors; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology*; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity*
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse