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

Fiche publication

Date publication

juillet 2025

Journal

Microbes and infection

Auteurs

Membres identifiés du Cancéropôle Est :
Mme DEMAIS Valérie , Mr HAMMANN Philippe

Tous les auteurs :
Skerniskyte J, Barroso MV, Chicher J, Hammann P, Demais V, Wright K, Mostowy S, Marteyn BS

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40617315

Résumé

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.