Host inflammatory response to mosquito bites enhances the severity of arbovirus infection

Pingen, M., Bryden, S. R., Pondeville, E., Schnettler, E., Kohl, A. , Merits, A., Fazakerley, J. K., Graham, G. J. and McKimmie, C. S. (2016) Host inflammatory response to mosquito bites enhances the severity of arbovirus infection. Immunity, 44(6), pp. 1455-1469. (doi:10.1016/j.immuni.2016.06.002) (PMID:27332734) (PMCID:PMC4920956)

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Abstract

Aedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schnettler, Dr Esther and McKimmie, Dr Clive and Pondeville, Dr Emilie and Pingen, Dr Marieke and Kohl, Professor Alain and Graham, Professor Gerard
Authors: Pingen, M., Bryden, S. R., Pondeville, E., Schnettler, E., Kohl, A., Merits, A., Fazakerley, J. K., Graham, G. J., and McKimmie, C. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunity
Publisher:Elsevier (Cell Press)
ISSN:1074-7613
ISSN (Online):1097-4180
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Immunity 44(6):1455-1469
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
560771Chemokine-mediated innate immune responses to arthropod bites and their virusesClive McKimmieMedical Research Council (MRC)G1001724III -IMMUNOLOGY