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A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin

Malaria remains one of the most serious health problems in developing countries. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. We recently found that γδ T...

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Autores principales: Hernández-Castañeda, Maria Andrea, Lavergne, Marilyne, Casanova, Pierina, Nydegger, Bryan, Merten, Carla, Subramanian, Bibin Yesodha, Matthey, Patricia, Lannes, Nils, Mantel, Pierre-Yves, Walch, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170093/
https://www.ncbi.nlm.nih.gov/pubmed/34093532
http://dx.doi.org/10.3389/fimmu.2021.643746
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author Hernández-Castañeda, Maria Andrea
Lavergne, Marilyne
Casanova, Pierina
Nydegger, Bryan
Merten, Carla
Subramanian, Bibin Yesodha
Matthey, Patricia
Lannes, Nils
Mantel, Pierre-Yves
Walch, Michael
author_facet Hernández-Castañeda, Maria Andrea
Lavergne, Marilyne
Casanova, Pierina
Nydegger, Bryan
Merten, Carla
Subramanian, Bibin Yesodha
Matthey, Patricia
Lannes, Nils
Mantel, Pierre-Yves
Walch, Michael
author_sort Hernández-Castañeda, Maria Andrea
collection PubMed
description Malaria remains one of the most serious health problems in developing countries. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. We recently found that γδ T cells control parasite growth using pore-forming proteins to deliver their cytotoxic proteases, the granzymes, into blood residing parasites. Here, we follow up on the molecular mechanisms of parasite growth inhibition by human pore-forming proteins. We confirm that Plasmodium falciparum infection efficiently depletes the red blood cells of cholesterol, which renders the parasite surrounding membranes susceptible to lysis by prokaryotic membrane disrupting proteins, such as lymphocytic granulysin or the human cathelicidin LL-37. Interestingly, not the cholesterol depletion but rather the simultaneous exposure of phosphatidylserine, a negatively charged phospholipid, triggers resistance of late stage parasitized red blood cells towards the eukaryotic pore forming protein perforin. Overall, by revealing the molecular events we establish here a pathogen-host interaction that involves host cell membrane remodeling that defines the susceptibility towards cytolytic molecules.
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spelling pubmed-81700932021-06-03 A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin Hernández-Castañeda, Maria Andrea Lavergne, Marilyne Casanova, Pierina Nydegger, Bryan Merten, Carla Subramanian, Bibin Yesodha Matthey, Patricia Lannes, Nils Mantel, Pierre-Yves Walch, Michael Front Immunol Immunology Malaria remains one of the most serious health problems in developing countries. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. We recently found that γδ T cells control parasite growth using pore-forming proteins to deliver their cytotoxic proteases, the granzymes, into blood residing parasites. Here, we follow up on the molecular mechanisms of parasite growth inhibition by human pore-forming proteins. We confirm that Plasmodium falciparum infection efficiently depletes the red blood cells of cholesterol, which renders the parasite surrounding membranes susceptible to lysis by prokaryotic membrane disrupting proteins, such as lymphocytic granulysin or the human cathelicidin LL-37. Interestingly, not the cholesterol depletion but rather the simultaneous exposure of phosphatidylserine, a negatively charged phospholipid, triggers resistance of late stage parasitized red blood cells towards the eukaryotic pore forming protein perforin. Overall, by revealing the molecular events we establish here a pathogen-host interaction that involves host cell membrane remodeling that defines the susceptibility towards cytolytic molecules. Frontiers Media S.A. 2021-05-19 /pmc/articles/PMC8170093/ /pubmed/34093532 http://dx.doi.org/10.3389/fimmu.2021.643746 Text en Copyright © 2021 Hernández-Castañeda, Lavergne, Casanova, Nydegger, Merten, Subramanian, Matthey, Lannes, Mantel and Walch https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hernández-Castañeda, Maria Andrea
Lavergne, Marilyne
Casanova, Pierina
Nydegger, Bryan
Merten, Carla
Subramanian, Bibin Yesodha
Matthey, Patricia
Lannes, Nils
Mantel, Pierre-Yves
Walch, Michael
A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
title A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
title_full A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
title_fullStr A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
title_full_unstemmed A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
title_short A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
title_sort profound membrane reorganization defines susceptibility of plasmodium falciparum infected red blood cells to lysis by granulysin and perforin
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170093/
https://www.ncbi.nlm.nih.gov/pubmed/34093532
http://dx.doi.org/10.3389/fimmu.2021.643746
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