Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions.
The last step of Leishmania intracellular life cycle is the egress of amastigotes from the host cell and their uptake by adjacent cells. Using multidimensional live imaging of long-term-infected macrophage cultures we observed that Leishmania amazonensis amastigotes were transferred from cell to cell when the donor host macrophage delivers warning signs of imminent apoptosis. They were extruded from the macrophage within zeiotic structures (membrane blebs, an apoptotic feature) rich in phagolysosomal membrane components. The extrusions containing amastigotes were selectively internalized by vicinal macrophages and the rescued amastigotes remain viable in recipient macrophages. Host cell apoptosis induced by micro-irradiation of infected macrophage nuclei promoted amastigotes extrusion, which were rescued by non-irradiated vicinal macrophages. Using amastigotes isolated from LAMP1/LAMP2 knockout fibroblasts, we observed that the presence of these lysosomal components on amastigotes increases interleukin 10 production. Enclosed within host cell membranes, amastigotes can be transferred from cell to cell without full exposure to the extracellular milieu, what represents an important strategy developed by the parasite to evade host immune system.
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brasil.
Fernando
F
Real
Pilar Tavares Veras
PT
Florentino
Luiza Campos
LC
Reis
Eduardo M
EM
Ramos-Sanchez
Patricia Sampaio Tavares
PS
Veras
Hiro
H
Goto
Renato Arruda
RA
Mortara
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000469:parasitology; D005347:Fibroblasts; D016753:Interleukin-10 / Q000096:biosynthesis; D007891:Leishmania / Q000472:pathogenicity*; D007896:Leishmaniasis / Q000473:pathology / Q000635:transmission*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D052118:Lysosomal-Associated Membrane Protein 1
D016753:Interleukin-10; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; C556062:IL10 protein, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1