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Title: Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
Authors: Fernandes, Maria Cecília Di Ciero [UNIFESP]
Cortez, Mauro
Flannery, Andrew R.
Tam, Christina
Mortara, Renato Arruda [UNIFESP]
Andrews, Norma W.
Univ Maryland
Universidade Federal de São Paulo (UNIFESP)
Issue Date: 9-May-2011
Publisher: Rockefeller Univ Press
Citation: Journal of Experimental Medicine. New York: Rockefeller Univ Press, v. 208, n. 5, p. 909-921, 2011.
Abstract: Upon host cell contact, the protozoan parasite Trypanosoma cruzi triggers cytosolic Ca(2+) transients that induce exocytosis of lysosomes, a process required for cell invasion. However, the exact mechanism by which lysosomal exocytosis mediates T. cruzi internalization remains unclear. We show that host cell entry by T. cruzi mimics a process of plasma membrane injury and repair that involves Ca(2+)-dependent exocytosis of lysosomes, delivery of acid sphingomyelinase ASM) to the outer leaflet of the plasma membrane, and a rapid form of endocytosis that internalizes membrane lesions. Host cells incubated with T. cruzi trypomastigotes are transiently wounded, show increased levels of endocytosis, and become more susceptible to infection when injured with pore-forming toxins. Inhibition or depletion of lysosomal ASM, which blocks plasma membrane repair, markedly reduces the susceptibility of host cells to T. cruzi invasion. Notably, extracellular addition of sphingomyelinase stimulates host cell endocytosis, enhances T. cruzi invasion, and restores normal invasion levels in ASM-depleted cells. Ceramide, the product of sphingomyelin hydrolysis, is detected in newly formed parasitophorous vacuoles containing trypomastigotes but not in the few parasite-containing vacuoles formed in ASM-depleted cells. Thus, T. cruzi subverts the ASM-dependent ceramide-enriched endosomes that function in plasma membrane repair to infect host cells.
ISSN: 0022-1007
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