MicroRNA-155 controls T helper cell activation during viral infection

Goncalves-Alves, E. et al. (2019) MicroRNA-155 controls T helper cell activation during viral infection. Frontiers in Immunology, 10, 1367. (doi: 10.3389/fimmu.2019.01367) (PMID:31275315) (PMCID:PMC6593301)

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Abstract

MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as autoimmune processes. Importantly, it has been shown to regulate several antiviral responses, but its contribution to the immune response against cytopathic viruses such as vesicular stomatitis virus (VSV) infections is not known. Using transgenic/recombinant VSV expressing ovalbumin, we show that miR-155 is crucially involved in regulating the T helper cell response against this virus. Our experiments indicate that miR-155 in CD4+ T cells controls their activation, proliferation, and cytokine production in vitro and in vivo upon immunization with OVA as well as during VSV viral infection. Using intravital multiphoton microscopy we analyzed the interaction of antigen presenting cells (APCs) and T cells after OVA immunization and found impaired complex formation when using miR-155 deficient CD4+ T cells compared to wildtype CD4+ T cells ex vivo. In contrast, miR-155 was dispensable for the maturation of myeloid APCs and for their T cell stimulatory capacity. Our data provide the first evidence that miR-155 is required for efficient CD4+ T cell activation during anti-viral defense by allowing robust APC-T cell interaction required for activation and cytokine production of virus specific T cells.

Item Type:Articles
Additional Information:This research has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement no 777357 (RTCure). During the writing of the manuscript, the first author was being funded by the Horizon 2020 Framework of the European Union in the CaSR Biomedicine project under grant agreement 675228. JSB is supported by the DOC fellowship of the Austrian Academy of Sciences.
Keywords:MicroRNA-155, antiviral immunity, T helper cells, T cell activation, APCs, APC-T cell interaction.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brewer, Professor James and Benson, Dr Robert and Kurowska-Stolarska, Dr Mariola
Authors: Goncalves-Alves, E., Saferding, V., Schliehe, C., Benson, R., Kurowska-Stolarska, M., Brunner, J. S., Puchner, A., Podesser, B. K., Smolen, J. S., Redlich, K., Bonelli, M., Brewer, J., Bergthaler, A., Steiner, G., and Blüml, S.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Immunology
Journal Abbr.:Front Immunol
Publisher:Frontiers Media
ISSN:1664-3224
ISSN (Online):1664-3224
Copyright Holders:Copyright © 2019 Goncalves-Alves, Saferding, Schliehe, Benson, KurowskaStolarska, Brunner, Puchner, Podesser, Smolen, Redlich, Bonelli, Brewer, Bergthaler, Steiner and Blüml
First Published:First published in Frontiers in Immunology 10: 1367
Publisher Policy:Reproduced under a Creative Commons License

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