Unveiling Leishmania invasion of fibroblasts: calcium signaling, lysosome recruitment and exocytosis culminate with actin-independent invasion.

摘要: Intracellular parasites of the genus Leishmania are causative agents human leishmaniasis, a widespread emergent tropical disease. The parasite is transmitted by bite sandfly vector that inoculates motile flagellated promastigote forms into dermis mammalian host. After inoculation, ultimately captured macrophages and multiply as round-shaped amastigote forms. Macrophages seem not to be first infected cells since were observed invading neutrophils whose leishmania-containing apoptotic bodies latter macrophages, thereby becoming infected. fact spp able live replicate inside immune phagocytic main cell type found in chronicity created perception passive players waiting phagocytes. However, several groups have described infection non-phagocytic vivo vitro. objective this work was study cellular mechanisms involved invasion non-professional phagocytes Leishmania. We show promastigotes L.amazonensis actively induces fibroblasts without cytoskeleton activity, thus through an induced phagocytosis previously proposed. Inside transformed amastigotes, remained viable for at least two weeks re-transformed when returned insect conditions. Similarly what T. cruzi, involves calcium signaling, recruitment exocytosis lysosomes lysosome-triggered endocytosis. Conditions alter lysosomal function such cytochalasin-D brefeldin-A treatment or knockout host proteins LAMP-1 2 dramatically affected invasion. Likewise, triggering lysosome-dependent plasma membrane repair low doses streptolysin-O increased entry. Together our results take advantage calcium-dependent lysosome-induced endocytosis invade persist cells.