Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

Melzi, E., Caporale, M., Rocchi, M., Martin, V., Gamino, V., di Provvido, A., Marruchella, G., Entrican, G., Sevilla, N. and Palmarini, M. (2016) Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression. Proceedings of the National Academy of Sciences of the United States of America, 113(41), E6238-E6247. (doi:10.1073/pnas.1610012113) (PMID:27671646) (PMCID:PMC5068271)

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Abstract

Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rocchi, Dr Mara and Melzi, Miss Eleonora and Palmarini, Professor Massimo and Entrican, Professor Gary and Caporale, Dr Marco
Authors: Melzi, E., Caporale, M., Rocchi, M., Martin, V., Gamino, V., di Provvido, A., Marruchella, G., Entrican, G., Sevilla, N., and Palmarini, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:26 September 2016
Copyright Holders:Copyright © 2016 National Academy of Sciences
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 2016
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
544121Phylogeography, transmission dynamics and pathogenesis of bluetongueMassimo PalmariniWellcome Trust (WELLCOME)092806/Z/10/ZMVLS III - CENTRE FOR VIRUS RESEARCH