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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.643746/full |
| _version_ | 1818387227713994752 |
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| author | Maria Andrea Hernández-Castañeda Marilyne Lavergne Pierina Casanova Bryan Nydegger Carla Merten Bibin Yesodha Subramanian Patricia Matthey Nils Lannes Pierre-Yves Mantel Michael Walch |
| author_facet | Maria Andrea Hernández-Castañeda Marilyne Lavergne Pierina Casanova Bryan Nydegger Carla Merten Bibin Yesodha Subramanian Patricia Matthey Nils Lannes Pierre-Yves Mantel Michael Walch |
| author_sort | Maria Andrea Hernández-Castañeda |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T04:06:36Z |
| format | Article |
| id | doaj.art-24765430ba404f48ad26508597b94715 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T04:06:36Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-24765430ba404f48ad26508597b947152022-12-21T23:17:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.643746643746A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and PerforinMaria Andrea Hernández-CastañedaMarilyne LavergnePierina CasanovaBryan NydeggerCarla MertenBibin Yesodha SubramanianPatricia MattheyNils LannesPierre-Yves MantelMichael WalchMalaria 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.643746/fullblood-stage malariapore forming proteins (PFPs)perforingranulysinplasma membranecholesterol |
| spellingShingle | Maria Andrea Hernández-Castañeda Marilyne Lavergne Pierina Casanova Bryan Nydegger Carla Merten Bibin Yesodha Subramanian Patricia Matthey Nils Lannes Pierre-Yves Mantel Michael Walch A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin Frontiers in Immunology blood-stage malaria pore forming proteins (PFPs) perforin granulysin plasma membrane cholesterol |
| 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 | blood-stage malaria pore forming proteins (PFPs) perforin granulysin plasma membrane cholesterol |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.643746/full |
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