Gilbert, A.S. orcid.org/0000-0002-1544-3862, Seoane, P.I. orcid.org/0000-0001-6323-5470, Sephton-Clark, P. orcid.org/0000-0003-1103-6028 et al. (12 more authors) (2017) Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5. Science Advances, 3 (8). e1700898. ISSN 2375-2548
Abstract
Vomocytosis, or nonlytic extrusion, is a poorly understood process through which macrophages release live pathogens that they have failed to kill back into the extracellular environment. Vomocytosis is conserved across vertebrates and occurs with a diverse range of pathogens, but to date, the host signaling events that underpin expulsion remain entirely unknown. We use a targeted inhibitor screen to identify the MAP kinase ERK5 as a critical suppressor of vomocytosis. Pharmacological inhibition or genetic manipulation of ERK5 activity significantly raises vomocytosis rates in human macrophages, whereas stimulation of the ERK5 signaling pathway inhibits vomocytosis. Lastly, using a zebrafish model of cryptococcal disease, we show that reducing ERK5 activity in vivo stimulates vomocytosis and results in reduced dissemination of infection. ERK5 therefore represents the first host signaling regulator of vomocytosis to be identified and a potential target for the future development of vomocytosis-modulating therapies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL C0494 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Sep 2017 14:46 |
Last Modified: | 06 Nov 2023 17:04 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Refereed: | Yes |
Identification Number: | 10.1126/sciadv.1700898 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:120814 |
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