Neutrophils display antibacterial defense via non-canonical LC3 decoration of extracellular bacteria

Jurate Skerniskyte ORCID logo ; Marina Valente Barroso ORCID logo ; Johana Chicher ; Philippe Hammann ; Valerie Demais ORCID logo ; Kathryn Wright ORCID logo ; Serge Mostowy ORCID logo ; Benoit S Marteyn ; (2025) Neutrophils display antibacterial defense via non-canonical LC3 decoration of extracellular bacteria. Microbes and infection / Institut Pasteur. p. 105545. ISSN 1286-4579 DOI: 10.1016/j.micinf.2025.105545 (In Press)
Copy

Neutrophils play a pivotal role in the innate immune response to bacterial infection, being one of the first immune cells to reach infectious sites. Bacterial infection may induce neutrophil degranulation, production of neutrophil extracellular traps (NETs), or pathogen phagocytosis. While LC3 is typically linked to autophagy, here we observed a non-canonical role of LC3 when peripheral neutrophils interact with bacteria both in vivo and in vitro, using Shigella spp. as a model. Upon incubation with neutrophils, extracellular bacteria became labelled by LC3 (LC3+) along with granules-localised antimicrobial components, such as lactotransferrin, defensin, elastase, and myeloperoxidase, as demonstrated by mass spectrometry. Co-localisation of LC3 and plasma membrane-specific dyes indicated that neutrophil plasma membrane-derived elongated structures covering bacteria were responsible for the labelling. This phenomenon was associated with bacterial growth restriction and bacterial cell-death induction. Testing with specific inhibitors demonstrated that this labelling was dependent on functional V-type ATP synthase. Covering bacteria with membrane-derived elongated structures enhanced the subsequent phagocytosis of bacteria by neutrophils. Finally, the LC3 labelling rate increased with higher bacterial burden. In conclusion, we propose that this defense mechanism is beneficial when the burden of bacterial infection overwhelms neutrophils' capacity for phagocytosis.

visibility_off picture_as_pdf

picture_as_pdf
Skerniskyte-etal-2025-Neutrophils-display-antibacterial-defense.pdf
subject
Published Version
lock
Restricted to Repository staff only
Available under Creative Commons: Attribution 4.0

Request Copy

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads