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Spatiotemporal dynamics of calcium signals during neutrophil cluster formation

Neutrophils form cellular clusters or swarms in response to injury or pathogen intrusion. Yet, intracellular signaling events favoring this coordinated response remain to be fully characterized. Here, we show that calcium signals play a critical role during mouse neutrophil clustering around particl...

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Autores principales: Khazen, Roxana, Corre, Béatrice, Garcia, Zacarias, Lemaître, Fabrice, Bachellier-Bassi, Sophie, d’Enfert, Christophe, Bousso, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308126/
https://www.ncbi.nlm.nih.gov/pubmed/35858359
http://dx.doi.org/10.1073/pnas.2203855119
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author Khazen, Roxana
Corre, Béatrice
Garcia, Zacarias
Lemaître, Fabrice
Bachellier-Bassi, Sophie
d’Enfert, Christophe
Bousso, Philippe
author_facet Khazen, Roxana
Corre, Béatrice
Garcia, Zacarias
Lemaître, Fabrice
Bachellier-Bassi, Sophie
d’Enfert, Christophe
Bousso, Philippe
author_sort Khazen, Roxana
collection PubMed
description Neutrophils form cellular clusters or swarms in response to injury or pathogen intrusion. Yet, intracellular signaling events favoring this coordinated response remain to be fully characterized. Here, we show that calcium signals play a critical role during mouse neutrophil clustering around particles of zymosan, a structural fungal component. Pioneer neutrophils recognizing zymosan or live Candida albicans displayed elevated calcium levels. Subsequently, a transient wave of calcium signals in neighboring cells was observed followed by the attraction of neutrophils that exhibited more persistent calcium signals as they reached zymosan particles. Calcium signals promoted LTB4 production while the blocking of extracellular calcium entry or LTB4 signaling abrogated cluster formation. Finally, using optogenetics to manipulate calcium influx in primary neutrophils, we show that calcium signals could initiate recruitment of neighboring neutrophils in an LTB4-dependent manner. Thus, sustained calcium responses at the center of the cluster are necessary and sufficient for the generation of chemoattractive gradients that attract neutrophils in a self-reinforcing process.
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spelling pubmed-93081262023-01-12 Spatiotemporal dynamics of calcium signals during neutrophil cluster formation Khazen, Roxana Corre, Béatrice Garcia, Zacarias Lemaître, Fabrice Bachellier-Bassi, Sophie d’Enfert, Christophe Bousso, Philippe Proc Natl Acad Sci U S A Biological Sciences Neutrophils form cellular clusters or swarms in response to injury or pathogen intrusion. Yet, intracellular signaling events favoring this coordinated response remain to be fully characterized. Here, we show that calcium signals play a critical role during mouse neutrophil clustering around particles of zymosan, a structural fungal component. Pioneer neutrophils recognizing zymosan or live Candida albicans displayed elevated calcium levels. Subsequently, a transient wave of calcium signals in neighboring cells was observed followed by the attraction of neutrophils that exhibited more persistent calcium signals as they reached zymosan particles. Calcium signals promoted LTB4 production while the blocking of extracellular calcium entry or LTB4 signaling abrogated cluster formation. Finally, using optogenetics to manipulate calcium influx in primary neutrophils, we show that calcium signals could initiate recruitment of neighboring neutrophils in an LTB4-dependent manner. Thus, sustained calcium responses at the center of the cluster are necessary and sufficient for the generation of chemoattractive gradients that attract neutrophils in a self-reinforcing process. National Academy of Sciences 2022-07-12 2022-07-19 /pmc/articles/PMC9308126/ /pubmed/35858359 http://dx.doi.org/10.1073/pnas.2203855119 Text en Copyright © 2022 the Author(s). Published by PNAS https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Khazen, Roxana
Corre, Béatrice
Garcia, Zacarias
Lemaître, Fabrice
Bachellier-Bassi, Sophie
d’Enfert, Christophe
Bousso, Philippe
Spatiotemporal dynamics of calcium signals during neutrophil cluster formation
title Spatiotemporal dynamics of calcium signals during neutrophil cluster formation
title_full Spatiotemporal dynamics of calcium signals during neutrophil cluster formation
title_fullStr Spatiotemporal dynamics of calcium signals during neutrophil cluster formation
title_full_unstemmed Spatiotemporal dynamics of calcium signals during neutrophil cluster formation
title_short Spatiotemporal dynamics of calcium signals during neutrophil cluster formation
title_sort spatiotemporal dynamics of calcium signals during neutrophil cluster formation
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308126/
https://www.ncbi.nlm.nih.gov/pubmed/35858359
http://dx.doi.org/10.1073/pnas.2203855119
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