Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites
Gasdermins (GSDMs) are a group of proteins that are cleaved by inflammatory caspases to induce pore formation in the plasma membrane to cause membrane permeabilization and lytic cell death or pyroptosis. All GSDMs share a conserved structure, containing a cytotoxic N-terminal (NT) pore-forming domai...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.900553/full |
| _version_ | 1811242863973892096 |
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| author | Shanshan Wang France Moreau Kris Chadee |
| author_facet | Shanshan Wang France Moreau Kris Chadee |
| author_sort | Shanshan Wang |
| collection | DOAJ |
| description | Gasdermins (GSDMs) are a group of proteins that are cleaved by inflammatory caspases to induce pore formation in the plasma membrane to cause membrane permeabilization and lytic cell death or pyroptosis. All GSDMs share a conserved structure, containing a cytotoxic N-terminal (NT) pore-forming domain and a C-terminal (CT) repressor domain. Entamoeba histolytica (Eh) in contact with macrophages, triggers outside-in signaling to activate inflammatory caspase-4/1 via the noncanonical and canonical pathway to promote cleavage of gasdermin D (GSDMD). Cleavage of GSDMD removes the auto-inhibition that masks the active pore-forming NT domain in the full-length protein by interactions with GSDM-CT. The cleaved NT-GSDMD monomers then oligomerize to form pores in the plasma membrane to facilitate the release of IL-1β and IL-18 with a measured amount of pyroptosis. Pyroptosis is an effective way to counteract intracellular parasites, which exploit replicative niche to avoid killing. To date, most GSDMs have been verified to perform pore-forming activity and GSDMD-induced pyroptosis is rapidly emerging as a mechanism of anti-microbial host defence. Here, we review our comprehensive and current knowledge on the expression, activation, biological functions, and regulation of GSDMD cleavage with emphases on physiological scenario and related dysfunctions of each GSDM member as executioner of cell death, cytokine secretion and inflammation against Eh and other protozoan parasitic infections. |
| first_indexed | 2024-04-12T13:57:18Z |
| format | Article |
| id | doaj.art-e880b574cf97436abf8a636bda5d1e79 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:57:18Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e880b574cf97436abf8a636bda5d1e792022-12-22T03:30:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.900553900553Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan ParasitesShanshan WangFrance MoreauKris ChadeeGasdermins (GSDMs) are a group of proteins that are cleaved by inflammatory caspases to induce pore formation in the plasma membrane to cause membrane permeabilization and lytic cell death or pyroptosis. All GSDMs share a conserved structure, containing a cytotoxic N-terminal (NT) pore-forming domain and a C-terminal (CT) repressor domain. Entamoeba histolytica (Eh) in contact with macrophages, triggers outside-in signaling to activate inflammatory caspase-4/1 via the noncanonical and canonical pathway to promote cleavage of gasdermin D (GSDMD). Cleavage of GSDMD removes the auto-inhibition that masks the active pore-forming NT domain in the full-length protein by interactions with GSDM-CT. The cleaved NT-GSDMD monomers then oligomerize to form pores in the plasma membrane to facilitate the release of IL-1β and IL-18 with a measured amount of pyroptosis. Pyroptosis is an effective way to counteract intracellular parasites, which exploit replicative niche to avoid killing. To date, most GSDMs have been verified to perform pore-forming activity and GSDMD-induced pyroptosis is rapidly emerging as a mechanism of anti-microbial host defence. Here, we review our comprehensive and current knowledge on the expression, activation, biological functions, and regulation of GSDMD cleavage with emphases on physiological scenario and related dysfunctions of each GSDM member as executioner of cell death, cytokine secretion and inflammation against Eh and other protozoan parasitic infections.https://www.frontiersin.org/articles/10.3389/fimmu.2022.900553/fullgasderminparasitemacrophageEntamoba histolyticainnate immunity |
| spellingShingle | Shanshan Wang France Moreau Kris Chadee Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites Frontiers in Immunology gasdermin parasite macrophage Entamoba histolytica innate immunity |
| title | Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites |
| title_full | Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites |
| title_fullStr | Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites |
| title_full_unstemmed | Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites |
| title_short | Gasdermins in Innate Host Defense Against Entamoeba histolytica and Other Protozoan Parasites |
| title_sort | gasdermins in innate host defense against entamoeba histolytica and other protozoan parasites |
| topic | gasdermin parasite macrophage Entamoba histolytica innate immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.900553/full |
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