@article{fd9dbe2794c046ed88dbe66da9a63b6e,
title = "Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5",
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.",
author = "Gilbert, {Andrew S.} and Seoane, {Paula I.} and Poppy Sephton-Clark and Aleksandra Bojarczuk and Richard Hotham and Emanuele Giurisato and Sarhan, {Adil R.} and Amy Hillen and Velde, {Greetje Vande} and Gray, {Nathanael S.} and Alessi, {Dario R.} and Cunningham, {Debbie L.} and Cathy Tournier and Johnston, {Simon A.} and May, {Robin C.}",
note = "A.S.G., P.I.S., and R.C.M. are supported by project MitoFun, funded by the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP/2007-2013)/ERC grant agreement no. 614562 and by a Wolfson Research Merit Award from the Royal Society (to R.C.M.), a Biotechnology and Biological Sciences Research Council Midlands Integrative Biosciences Training Partnership Studentship (to A.S.G.), and a scholarship from the Darwin Trust of Edinburgh (to P.I.S.). S.A.J. and A.B. were supported by Medical Research Council and Department for International Development Career Development Award Fellowship (MR/J009156/1). S.A.J. was additionally supported by a Krebs Institute Fellowship, the Medical Research Foundation (grant R/140419), and the Medical Research Council Center (grant G0700091). R.H. was supported by a Colin Beattie Biomedical Science scholarship. A.R.S. was supported by a scholarship from the Higher Committee for Education Development in Iraq. E.G. was supported by a Marie Curie Research Fellowship, and C.T. is supported by a grant from Worldwide Cancer Research. G.V.V. is supportedby a postdoctoral grant from the Flemish Research Foundation. D.R.A. acknowledges funding from the UK Medical Research Council (grant number MC-UU_1201612).",
year = "2017",
month = aug,
day = "16",
doi = "10.1126/sciadv.1700898",
language = "English",
volume = "3",
pages = "1--9",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "8",
}