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

Melzi, Eleonora (2017) Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.

Abstract

Arboviruses (Arthropod-borne viruses) cause acute diseases that are increasingly affecting both human and animal health. Currently, there is a critical lack of understanding about the nature of arbovirus-host interactions in the lymph nodes (LNs), the place where the adaptive immune response is initiated and shaped. In this study, we used bluetongue virus (BTV) and its natural sheep host, to characterise the early events of an arbovirus infection with particular focus on the LNs. Our findings reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. This 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 the stromal network of marginal reticular cells and follicular dendritic cells composing the scaffolding of the follicular area. These cells contribute to antigen presentation and affinity maturation of B-cells for the production of antibodies. Consequently, we observed a loss of germinal centre structure, which hinders B-cell proliferation. This process results in a delayed production of high affinity and virus neutralizing antibodies that is directly related to the virulence of the BTV strain used and the severity of disease. Moreover the humoral immune response to a different antigen is also hampered in BTV-infected animals. Our data show that an arbovirus can evade the host antiviral responses 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: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Bluetongue, follicular dendritic cells, immunology, virology, lymph node, immunosuppression, arbovirus, stromal cells.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Funder's Name: UNSPECIFIED
Supervisor's Name: Palmarini, Professor Massimo
Date of Award: 2017
Embargo Date: 17 January 2019
Depositing User: Dr Eleonora Melzi
Unique ID: glathesis:2017-7870
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 18 Jan 2017 10:14
Last Modified: 07 Feb 2017 13:16
URI: http://theses.gla.ac.uk/id/eprint/7870

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