VAMP3 and VAMP8 Regulate the Development and Functionality of Parasitophorous Vacuoles Housing Leishmania amazonensis

Abstract

To colonize mammalian phagocytic cells, the parasite Leishmania remodels phagosomes into parasitophorous vacuoles that can be either tight-fitting individual or communal. The molecular and cellular bases underlying the biogenesis and functionality of these two types of vacuoles are poorly understood. In this study, we investigated the contribution of host cell Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor proteins to the expansion and functionality of communal vacuoles as well as on the replication of the parasite. The differential recruitment patterns of Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor to communal vacuoles harboring L. amazonensis and to individual vacuoles housing L. major led us to further investigate the roles of VAMP3 and VAMP8 in the interaction of Leishmania with its host cell. We show that whereas VAMP8 contributes to optimal expansion of communal vacuoles, VAMP3 negatively regulates L. amazonensis replication, vacuole size, as well as antigen cross-presentation. In contrast, neither proteins has an impact on the fate of L. major . Collectively, our data support a role for both VAMP3 and VAMP8 in the development and functionality of L. amazonensis -harboring communal parasitophorous vacuoles.

Leishmania amazonensis sabotages host cell SUMOylation for intracellular survival

“…These last two findings suggests that this alternate V-ATPase subunit function could be involved in PV biogenenesis by controlling vesicular membrane fusion. One interesting hypothesis is that ATP6V0D2 interacts with VAMP8 to promote fusion of endocytic organelles to Leishmania PVs, as interaction of ATP6V0D2 with VAMP8 has been shown to control autophagosome-lysosome fusion during S. typhimurium infection (Furuta et al, 2010) whereas VAMP8 is also linked to fusion of endocytic vesicles the L. amazonensis PV (Seguin et al, 2022).…”

Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology

“…Silencing of VAMP3 affects the migration of cells and cell-mediated adhesion by integrin ( Luftman et al., 2009 ). Furthermore, in the human parasite Leishmania amazonensis , VAMP3 has an important function in the formation of parasitophorous vacuoles ( Séguin et al., 2022 ). In the case of malaria parasite, Plasmodium falciparum vesicle-mediated trafficking transports parasite proteins into the infected host cytosol and cell membrane ( Taraschi et al., 2001 ).…”