Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts alteration in macrophages from patients with cystic fibrosis

Manuella Lévêque (1) , Aubin Penna (1) , Sophie Le Trionnaire (1) , Chantal Belleguic (2) , Benoit Desrues (2, 3) , Graziella Brinchault (2) , Stéphane Jouneau (2, 1) , Dominique Lagadic-Gossmann (1) , Corinne Martin-Chouly (1)

1 Irset - Institut de recherche en santé, environnement et travail
2 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
3 COSS - Chemistry, Oncogenesis, Stress and Signaling

Whereas many phagocytosis steps involve ionic fluxes, the underlying ion channels remain poorly defined. As reported in mice, the calcium conducting TRPV2 channel impacts the phagocytic process. Macrophage phagocytosis is critical for defense against pathogens. In cystic fibrosis (CF), macrophages have lost their capacity to act as suppressor cells and thus play a significant role in the initiating stages leading to chronic inflammation/infection. In a previous study, we demonstrated that impaired function of CF macrophages is due to a deficient phagocytosis. The aim of the present study was to investigate TRPV2 role in the phagocytosis capacity of healthy primary human macrophage by studying its activity, its membrane localization and its recruitment in lipid rafts. In primary human macrophages, we showed that P. aeruginosa recruits TRPV2 channels at the cell surface and induced a calcium influx required for bacterial phagocytosis. We presently demonstrate that to be functional and play a role in phagocytosis, TRPV2 might require a preferential localization in lipid rafts. Furthermore, CF macrophage displays a perturbed calcium homeostasis due to a defect in TRPV2. In this context, deregulated TRPV2-signaling in CF macrophages could explain their defective phagocytosis capacity that contribute to the maintenance of chronic infection.

Domaines: Santé publique et épidémiologie

Manuella Lévêque, Aubin Penna, Sophie Le Trionnaire, Chantal Belleguic, Benoit Desrues, et al.. Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts alteration in macrophages from patients with cystic fibrosis. Scientific Reports, 2018, 8 (1), pp.4310. ⟨10.1038/s41598-018-22558-5⟩. ⟨hal-01744220⟩