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Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion

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...

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Autores principales: Fernandes, Maria Cecilia, Cortez, Mauro, Flannery, Andrew R., Tam, Christina, Mortara, Renato A., Andrews, Norma W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092353/
https://www.ncbi.nlm.nih.gov/pubmed/21536739
http://dx.doi.org/10.1084/jem.20102518
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author Fernandes, Maria Cecilia
Cortez, Mauro
Flannery, Andrew R.
Tam, Christina
Mortara, Renato A.
Andrews, Norma W.
author_facet Fernandes, Maria Cecilia
Cortez, Mauro
Flannery, Andrew R.
Tam, Christina
Mortara, Renato A.
Andrews, Norma W.
author_sort Fernandes, Maria Cecilia
collection PubMed
description 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.
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spelling pubmed-30923532011-11-09 Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion Fernandes, Maria Cecilia Cortez, Mauro Flannery, Andrew R. Tam, Christina Mortara, Renato A. Andrews, Norma W. J Exp Med Article 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. The Rockefeller University Press 2011-05-09 /pmc/articles/PMC3092353/ /pubmed/21536739 http://dx.doi.org/10.1084/jem.20102518 Text en © 2011 Fernandes et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Fernandes, Maria Cecilia
Cortez, Mauro
Flannery, Andrew R.
Tam, Christina
Mortara, Renato A.
Andrews, Norma W.
Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
title Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
title_full Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
title_fullStr Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
title_full_unstemmed Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
title_short Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
title_sort trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092353/
https://www.ncbi.nlm.nih.gov/pubmed/21536739
http://dx.doi.org/10.1084/jem.20102518
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