Leishmania amazonensis hijacks host cell lysosomes involved in plasma membrane repair to induce invasion in fibroblasts

• DOI: 10.1242/jcs.226183
• Publication Date: 2019-02-27T14:34:47Z
• Authors: Victor Soares Cav...; Mariana Costa-Reg...; Thamires Queiroz-...; Anny C. S. Oliveira; Natália Fernanda ...; Danielle Oliveira...; Jane Lima-Santos; Luciana Oliveira ...; Maria Fátima Horta; Thiago Castro-Gomes
• Keywords: 0301 basic medicine; Macrophages; Cell Membrane; Leishmania mexicana; Fibroblasts; Exocytosis; Cell Line; Host-Parasite Interactions; 3. Good health; Actin Cytoskeleton; Mice; 03 medical and health sciences; Phagocytosis; Animals; Calcium Signaling; Lysosomes

ABSTRACT Intracellular parasites of the genus Leishmania are the causative agents of leishmaniasis. The disease is transmitted by the bite of a sand fly vector, which inoculates the parasite into the skin of mammalian hosts, including humans. During chronic infection the parasite lives and replicates inside phagocytic cells, notably the macrophages. An interesting, but overlooked finding, is that other cell types and even non-phagocytic cells have been found to be infected by Leishmania spp. Nevertheless, the mechanisms by which Leishmania invades such cells had not been previously studied. Here, we show that L. amazonensis can induce their own entry into fibroblasts independently of actin cytoskeleton activity, and, thus, through a mechanism that is distinct from phagocytosis. Invasion involves subversion of host cell functions, such as Ca2+ signaling and recruitment and exocytosis of host cell lysosomes involved in plasma membrane repair. This article has an associated First Person interview with the first author of the paper.