Séguin, Olivier et Descoteaux, Albert . VAMP3 as a negative regulator of Leishmania amazonensis infection and antigen cross-presentation In: the Annual Meeting of the American-Association-of-Immunologists - Immunology 2020, 8-12 July 2020, Honolulu, HI.
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To colonize host immune cells, the protozoan parasite Leishmania creates a parasitophorous vacuole (PV) that can be either individual and tight-fitting or communal, large and spacious depending on the parasite species. We aimed to investigate the role of SNAREs in both PV formation and parasite survival. Using bone marrow-derived macrophages (BMM) and confocal microscopy, we found that L. amazonensis communal PV recruits SNAREs and membrane from the plasma membrane (SNAP23), the recycling endosome (VAMP3), the endoplasmic reticulum (STX18) and the trans-golgi (Vti1a) with fusion with the lysosomes (LAMP1) while only the late endosomes (VAMP8) are accumulated to L. major individual PV without fusion with the lysosome. In the absence of VAMP3 we found that replication of L. amazonensis and PV volume roughly doubled. The V0 subunit of the V-ATPase has been proposed as a fusion promoter and as anti-inflammatory. More recently, the V0 subunit was shown to controls Leishmania PV biogenesis via cholesterol homeostasis. We then linked the PV volume augmentation to an augmented V-ATPase V0 subunit TCIRG1. We verified the inflammatory capacity of VAMP3 KO BMMs and found that NO production reduced. IFN-ɣ and LPS stimulated VAMP3 KO BMMs killing capacity was also halved during L. amazonensis infection. Furthermore, cholesterol homeostasis was also shown to play a role in antigen presentation and we found that VAMP3 KO BMDCs had augmented antigen cross-presentation capacities. In conclusion, we report that VAMP3 acts as a negative regulator of L. amazonensis replication by limiting cholesterol availability and through its role in limiting the availability of the V0 subunit of the V-ATPase.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Informations complémentaires: | Affiche scientifique P740 Journal of Immunology 204 (suppl 1) 231.6 https://www.jimmunol.org/content/204/1_Supplement/231.6 |
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 14 juill. 2021 15:50 |
| Dernière modification: | 14 juill. 2021 15:50 |
| URI: | https://espace.inrs.ca/id/eprint/11819 |
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