Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions

Autor(es)

Real, Fernando ^[1] ; Veras Florentino, Pilar Tavares ^[1] ; Reis, Luiza Campos ^[2] ; Ramos-Sanchez, Eduardo M. ^[2] ; Tavares Veras, Patricia Sampaio ^[3] ; Goto, Hiro ^{[2, 4]} ; Mortara, Renato Arruda ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Escola Paulista Medi, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Inst Trop Med, Lab Soroepidemiol & Imunobiol, Sao Paulo - Brazil

^[3] Fdn Oswaldo Cruz FIOCRUZ, INCT DT, Salvador - Brazil

^[4] Univ Fed Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cellular Microbiology; v. 16, n. 10, p. 1549-1564, OCT 2014.
• Citações Web of Science: 21

Resumo

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. (AU)

• Processo FAPESP: 10/19335-4 - Estudo dos mecanismos de fusão entre vacúolos parasitóforos heterotípicos de Leishmania spp.
• Beneficiário: Fernando Roberto Oliveira Real
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado