Cargando…

Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses

Neutrophils influence innate and adaptive immunity by releasing various cytokines and chemokines, by generating neutrophil extracellular traps (NETs), and by modulating their own survival. Neutrophils also produce extracellular vesicles (EVs) termed ectosomes, which influence the function of other i...

Descripción completa

Detalles Bibliográficos
Autores principales: Hurtado Gutiérrez, María José, Allard, Frédérick L., Mosha, Hugo Tshivuadi, Dubois, Claire M., McDonald, Patrick P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818892/
https://www.ncbi.nlm.nih.gov/pubmed/36611930
http://dx.doi.org/10.3390/cells12010136
_version_ 1784865097218260992
author Hurtado Gutiérrez, María José
Allard, Frédérick L.
Mosha, Hugo Tshivuadi
Dubois, Claire M.
McDonald, Patrick P.
author_facet Hurtado Gutiérrez, María José
Allard, Frédérick L.
Mosha, Hugo Tshivuadi
Dubois, Claire M.
McDonald, Patrick P.
author_sort Hurtado Gutiérrez, María José
collection PubMed
description Neutrophils influence innate and adaptive immunity by releasing various cytokines and chemokines, by generating neutrophil extracellular traps (NETs), and by modulating their own survival. Neutrophils also produce extracellular vesicles (EVs) termed ectosomes, which influence the function of other immune cells. Here, we studied neutrophil-derived ectosomes (NDEs) and whether they can modulate autologous neutrophil responses. We first characterized EV production by neutrophils, following MISEV 2018 guidelines to facilitate comparisons with other studies. We found that such EVs are principally NDEs, that they are rapidly released in response to several (but not all) physiological stimuli, and that a number of signaling pathways are involved in the induction of this response. When co-incubated with autologous neutrophils, NDE constituents were rapidly incorporated into recipient cells and this triggered and/or modulated neutrophil responses. The pro-survival effect of GM-CSF, G-CSF, IFNγ, and dexamethasone was reversed; CXCL8 and NET formation were induced in otherwise unstimulated neutrophils; the induction of inflammatory chemokines by TNFα was modulated depending on the activation state of the NDEs’ parent cells; and inducible NET generation was attenuated. Our data show that NDE generation modulates neutrophil responses in an autocrine and paracrine manner, and indicate that this probably represents an important aspect of how neutrophils shape their environment and cellular interactions.
format Online
Article
Text
id pubmed-9818892
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98188922023-01-07 Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses Hurtado Gutiérrez, María José Allard, Frédérick L. Mosha, Hugo Tshivuadi Dubois, Claire M. McDonald, Patrick P. Cells Article Neutrophils influence innate and adaptive immunity by releasing various cytokines and chemokines, by generating neutrophil extracellular traps (NETs), and by modulating their own survival. Neutrophils also produce extracellular vesicles (EVs) termed ectosomes, which influence the function of other immune cells. Here, we studied neutrophil-derived ectosomes (NDEs) and whether they can modulate autologous neutrophil responses. We first characterized EV production by neutrophils, following MISEV 2018 guidelines to facilitate comparisons with other studies. We found that such EVs are principally NDEs, that they are rapidly released in response to several (but not all) physiological stimuli, and that a number of signaling pathways are involved in the induction of this response. When co-incubated with autologous neutrophils, NDE constituents were rapidly incorporated into recipient cells and this triggered and/or modulated neutrophil responses. The pro-survival effect of GM-CSF, G-CSF, IFNγ, and dexamethasone was reversed; CXCL8 and NET formation were induced in otherwise unstimulated neutrophils; the induction of inflammatory chemokines by TNFα was modulated depending on the activation state of the NDEs’ parent cells; and inducible NET generation was attenuated. Our data show that NDE generation modulates neutrophil responses in an autocrine and paracrine manner, and indicate that this probably represents an important aspect of how neutrophils shape their environment and cellular interactions. MDPI 2022-12-29 /pmc/articles/PMC9818892/ /pubmed/36611930 http://dx.doi.org/10.3390/cells12010136 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hurtado Gutiérrez, María José
Allard, Frédérick L.
Mosha, Hugo Tshivuadi
Dubois, Claire M.
McDonald, Patrick P.
Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses
title Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses
title_full Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses
title_fullStr Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses
title_full_unstemmed Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses
title_short Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses
title_sort human neutrophils generate extracellular vesicles that modulate their functional responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818892/
https://www.ncbi.nlm.nih.gov/pubmed/36611930
http://dx.doi.org/10.3390/cells12010136
work_keys_str_mv AT hurtadogutierrezmariajose humanneutrophilsgenerateextracellularvesiclesthatmodulatetheirfunctionalresponses
AT allardfrederickl humanneutrophilsgenerateextracellularvesiclesthatmodulatetheirfunctionalresponses
AT moshahugotshivuadi humanneutrophilsgenerateextracellularvesiclesthatmodulatetheirfunctionalresponses
AT duboisclairem humanneutrophilsgenerateextracellularvesiclesthatmodulatetheirfunctionalresponses
AT mcdonaldpatrickp humanneutrophilsgenerateextracellularvesiclesthatmodulatetheirfunctionalresponses