Neutrophil Extracellular Traps Induced by VP1 Contribute to Pulmonary Edema During EV71 Infection

Overview

Journal Cell Death Discov

Date 2019 Jul 10

PMID 31285854

Citations 11

Authors

Nan Wang

Xiaofan Yang

Jiandong Sun

Zhixiao Sun

Qiyun Ma

Zhengxia Wang

Zhongqi Chen

Zibin Wang

Fan Hu

Huijuan Wang

Linfu Zhou

Mingshun Zhang

Juan Xu

Affiliations

Soon will be listed here.

Abstract

Pulmonary edema is a fatal complication of EV71-associated hand, foot, and mouth disease (HFMD). The pathogenesis of EV71-induced pulmonary edema remains largely unclear. In this study, we aimed to explore the roles of the capsid protein VP1 in the occurrence of EV71-induced pulmonary edema. The intranasal inoculation of recombinant VP1 protein caused lung inflammation with an elevation of inflammatory cytokines and neutrophils infiltration. Moreover, neutrophil extracellular traps (NETs) were observed in the lung parenchyma of the mice treated with VP1. VP1 directly induced the formation of NETs, which depended on PAD4. VP1 also damaged the lung barrier via the reduction of the tight junction protein occludin. Moreover, the EV71 attachment receptor vimentin was increased upon VP1 administration. In contrast, NETs decreased vimentin levels, suggesting a novel role for NETs in viral immune defense. These results evidenced a direct role of VP1 in EV71-induced pulmonary edema and demonstrated that NETs may be both harmful and beneficial in EV71 infection.

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