VAMP3 and VAMP8 regulate the development and functionality of parasitophorous vacuoles housingLeishmania amazonensis

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>To colonize mammalian phagocytic cells, the parasite <jats:italic>Leishmania</jats:italic> 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 in 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 <jats:italic>L. amazonensis</jats:italic> and to individual vacuoles housing <jats:italic>L. major</jats:italic> led us to further investigate the contribution of VAMP3 and VAMP8 in the interaction of <jats:italic>Leishmania</jats:italic> with its host cell. We show that whereas VAMP8 contributes to optimal expansion of communal vacuoles, VAMP3 negatively regulates <jats:italic>L. amazonensis</jats:italic> replication, vacuole size, as well as antigen cross-presentation. In contrast, neither proteins has an impact on the fate of <jats:italic>L. major</jats:italic>. Collectively, our data support a role for both VAMP3 and VAMP8 in the development and functionality of <jats:italic>L. amazonensis</jats:italic>-harboring communal parasitophorous vacuoles.</jats:p>