A subset of neutrophil phagosomes is characterised by pulses of Class I PI3K activity.
| Title: | A subset of neutrophil phagosomes is characterised by pulses of Class I PI3K activity. |
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| Authors: | Muir CF; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK.; Centre of Inflammation, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.; Reyes-Aldasoro CC; Department of Computer Science, School of Science and Technology, City, University of London, London EC1V 0HB, UK.; Prajsnar TK; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków 30-387, Poland.; Michno BJ; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków 30-387, Poland.; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków 30-348, Poland.; Cholewa-Waclaw J; Centre of Inflammation, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.; Ho YX; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; Bernut A; Laboratory of Pathogens and Host Immunity, Université de Montpellier, Montpellier 34090, France.; Loynes CA; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; Elworthy S; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; Bowden KA; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; Cadby AJ; Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.; Prince LR; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; King JS; School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.; Ellett F; Centre for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Hospital, Boston, MA 02114, USA.; Condliffe AM; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK.; Renshaw SA; Bateson Centre, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, UK. |
| Source: | Disease models & mechanisms [Dis Model Mech] 2025 Sep 01; Vol. 18 (9). Date of Electronic Publication: 2025 Aug 29. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Cambridge : Company of Biologists Ltd., c2008- |
| MeSH Terms: | Phagosomes*/enzymology ; Phagosomes*/metabolism ; Neutrophils*/enzymology ; Neutrophils*/microbiology ; Class I Phosphatidylinositol 3-Kinases*/metabolism; Zebrafish/microbiology ; Phosphatidylinositol Phosphates/metabolism ; Green Fluorescent Proteins/metabolism ; Animals ; Humans ; Signal Transduction ; Phagocytosis |
| Abstract: | Class I PI3 kinases (PI3Ks) coordinate the delivery of microbicidal effectors to the phagosome by forming phosphatidylinositol (3,4,5)-trisphosphate (PIP3). However, the dynamics of PIP3 in neutrophils during a live bacterial tissue infection are unknown. We therefore developed an in vivo, live zebrafish infection model that enables visualisation of dynamic changes in Class 1 PI3K signalling in neutrophil phagosomes in real time. We identified that, on ∼12% of neutrophil phagosomes, PHAkt-eGFP, a reporter for Class 1 PI3K signalling, repeatedly fades and re-recruits in pulsatile bursts. This phenomenon occurred on phagosomes containing live and dead bacteria as well as beads, and was dependent on the activity of the Class 1 PI3K isoform PI3Kγ. Detailed imaging suggested that pulsing phagosomes represent neutrophils transiently re-opening and re-closing phagosomes, a conclusion supported by observations that a subset of phagosomes in human neutrophils rapidly accumulate dye from the extracellular space. Therefore, we propose that some neutrophil phagosomes remain unsealed and are consequently able to exchange contents with the extracellular environment, with implications for phagosome fate and communication with surrounding cells.; (© 2025. Published by The Company of Biologists.) |
| Competing Interests: | Competing interests The authors declare no competing or financial interests. |
| Comments: | Erratum in: Dis Model Mech. 2025 Oct 1;18(10):dmm052685. doi: 10.1242/dmm.052685.. (PMID: 41123561) |
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| Grant Information: | UMO-2019/34/E/NZ6/00137 Narodowe Centrum Nauki; B/V019368/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; University of Sheffield; United Kingdom WT_ Wellcome Trust; R/151624 United Kingdom WT_ Wellcome Trust; (R/151624 United Kingdom WT_ Wellcome Trust |
| Contributed Indexing: | Keywords: Neutrophils; Phagocytosis; Phagosome maturation; Phosphatidylinositol (3,4,5)-trisphosphate; Zebrafish |
| Substance Nomenclature: | EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases); 0 (Phosphatidylinositol Phosphates); 147336-22-9 (Green Fluorescent Proteins) |
| Entry Date(s): | Date Created: 20250722 Date Completed: 20250829 Latest Revision: 20251022 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12444860 |
| DOI: | 10.1242/dmm.052042 |
| PMID: | 40692416 |
| Database: | MEDLINE |
Journal Article