Cell-to-cell transfer of Leishmania amazonensis amastigotes is mediated by immunomodulatory LAMP-rich parasitophorous extrusions
2014
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.
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