Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton

The inflammasome is a complex present in the cytosol of stimulated immune cells that leads\nto the activation of pro-inflammatory caspase-1. Active caspase-1 is responsible for the release\nof the pro-inflammatory interleukin-1? (IL-1?) and IL-18, and cleavage of Gasdermin-D, which\nultimately resul...

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Autor principal: Rincón, María Gabriela
Otros Autores: Radice, Marcela
Formato: Tesis de maestría acceptedVersion
Lenguaje:Inglés
Publicado: Facultad de Farmacia y Bioquímica 2019
Materias:
Inflamasomainducida
Inflammasome
Clostridium difficile
Cytoskeleton
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5944
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5944.dir/5944.PDF
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
id I28-R145-HWA_5944
record_format dspace
spelling I28-R145-HWA_59442022-04-18 The inflammasome is a complex present in the cytosol of stimulated immune cells that leads\nto the activation of pro-inflammatory caspase-1. Active caspase-1 is responsible for the release\nof the pro-inflammatory interleukin-1? (IL-1?) and IL-18, and cleavage of Gasdermin-D, which\nultimately results in a form of lytic cell death known as pyroptosis. Clostridium difficile is an\nanaerobe, spore-forming bacterium that can cause antibiotic-related diarrhea and\npseudomembranous colitis. Major virulence factors of this pathogen are the Rho-glycosylating\ntoxins A and B (TcdA, TcdB), which inactivate Rho-GTPases. Hyper virulent strains of\nClostridium difficile also produce the binary toxin C. difficile transferase (CDT). CDT ADPribosylates\nmonomeric G-actin resulting in complete depolymerization of the actin\ncytoskeleton. Previously, first studies about the influence of TcdA and TcdB onr inflammasome\nactivation have been reported. Morer recently, it was identified that Pyrin, a protein capable of\nassembling the inflammasome, acts as a sensor responsible for detecting the inactivation of\nRho GTPases. Since no direct binding of the modified GTPases to Pyrin was observed, the\nauthors concluded that Pyrin likely senses the effects of GTPase inactivation on the actin\ncytoskeleton. Interactions of Pyrin and other ?receptors? activating the inflammasome with\ncomponents of the cytoskeleton indicate that alteration of cytoskeletal dynamics plays an\nimportant role in inflammasome activation. Considering this, we decided to evaluate if CDT\ncould activate the inflammasome, and to further characterize inflammasome activation by\nTcdB. Our results show that both TcdB and CDT are capable of inducing ASC speck formation\nand release of IL-1? from competent immune cells. TcdB also induced activation of caspase-\n1 and pyroptosis, and we found evidence that TcdB influences several receptors involved in\ninflammasome assembly. This data confirm the important role of clostridial toxins that target\nthe cytoskeleton in exerting inflammatory responses in the host. Fil: Rincón, María Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Radice, Marcela Facultad de Farmacia y Bioquímica Aktories, Klaus Rincón, María Gabriela 2019-03-26 application/pdf Cerquetti, Cristina Hozbor, Daniela Borner, Christoph Inflamasomainducida Inflammasome Clostridium difficile Cytoskeleton eng Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5944 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5944.dir/5944.PDF
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Inglés
orig_language_str_mv eng
topic Inflamasomainducida
Inflammasome
Clostridium difficile
Cytoskeleton
Ciencias de la vida
spellingShingle Inflamasomainducida
Inflammasome
Clostridium difficile
Cytoskeleton
Ciencias de la vida
Rincón, María Gabriela
Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
topic_facet Inflamasomainducida
Inflammasome
Clostridium difficile
Cytoskeleton
Ciencias de la vida
description The inflammasome is a complex present in the cytosol of stimulated immune cells that leads\nto the activation of pro-inflammatory caspase-1. Active caspase-1 is responsible for the release\nof the pro-inflammatory interleukin-1? (IL-1?) and IL-18, and cleavage of Gasdermin-D, which\nultimately results in a form of lytic cell death known as pyroptosis. Clostridium difficile is an\nanaerobe, spore-forming bacterium that can cause antibiotic-related diarrhea and\npseudomembranous colitis. Major virulence factors of this pathogen are the Rho-glycosylating\ntoxins A and B (TcdA, TcdB), which inactivate Rho-GTPases. Hyper virulent strains of\nClostridium difficile also produce the binary toxin C. difficile transferase (CDT). CDT ADPribosylates\nmonomeric G-actin resulting in complete depolymerization of the actin\ncytoskeleton. Previously, first studies about the influence of TcdA and TcdB onr inflammasome\nactivation have been reported. Morer recently, it was identified that Pyrin, a protein capable of\nassembling the inflammasome, acts as a sensor responsible for detecting the inactivation of\nRho GTPases. Since no direct binding of the modified GTPases to Pyrin was observed, the\nauthors concluded that Pyrin likely senses the effects of GTPase inactivation on the actin\ncytoskeleton. Interactions of Pyrin and other ?receptors? activating the inflammasome with\ncomponents of the cytoskeleton indicate that alteration of cytoskeletal dynamics plays an\nimportant role in inflammasome activation. Considering this, we decided to evaluate if CDT\ncould activate the inflammasome, and to further characterize inflammasome activation by\nTcdB. Our results show that both TcdB and CDT are capable of inducing ASC speck formation\nand release of IL-1? from competent immune cells. TcdB also induced activation of caspase-\n1 and pyroptosis, and we found evidence that TcdB influences several receptors involved in\ninflammasome assembly. This data confirm the important role of clostridial toxins that target\nthe cytoskeleton in exerting inflammatory responses in the host.
author2 Radice, Marcela
author_facet Radice, Marcela
Rincón, María Gabriela
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Rincón, María Gabriela
author_sort Rincón, María Gabriela
title Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
title_short Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
title_full Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
title_fullStr Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
title_full_unstemmed Activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
title_sort activation of the inflammasome by bacterial protein toxins targeting the cytoskeleton
publisher Facultad de Farmacia y Bioquímica
publishDate 2019
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5944
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5944.dir/5944.PDF
work_keys_str_mv AT rinconmariagabriela activationoftheinflammasomebybacterialproteintoxinstargetingthecytoskeleton
_version_ 1766017555882835968

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