Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection

Autores
Giai, Constanza; Gonzalez, Cintia Daniela; Ledo, Camila; Garofalo, Ailin Natalia; Di Genaro, Maria Silvia; Sordelli, Daniel Oscar; Gomez, Marisa Ines
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Staphylococcus aureus infections are an important concern in public health due to their increasing incidence and high rates of mortality. The S. aureus success as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of TNF-alpha in the initial host defense against staphylococcal systemic infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-alpha receptor (TNFR1). In this study, we demonstrate that S. aureus, via protein A mediated signaling, induces early shedding of soluble TNFR1 which precedes the secretion of TNF-alpha in vitro and in vivo. The results obtained using a protein A deficient mutant and tnfr1-/- mice strongly suggest that the increased levels of soluble TNFR1 present during S. aureus experimental infection may neutralize circulating TNF-alpha and impair the host inflammatory response. Early shedding of soluble TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response.
Fil: Giai, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Gonzalez, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Ledo, Camila. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina
Fil: Garofalo, Ailin Natalia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina
Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Gomez, Marisa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Materia
Staphylococcus Aureus
Protein A
Tnf-Alpha
Inflammation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/6594
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/6594
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infectionGiai, ConstanzaGonzalez, Cintia DanielaLedo, CamilaGarofalo, Ailin NataliaDi Genaro, Maria SilviaSordelli, Daniel OscarGomez, Marisa InesStaphylococcus AureusProtein ATnf-AlphaInflammationhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Staphylococcus aureus infections are an important concern in public health due to their increasing incidence and high rates of mortality. The S. aureus success as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of TNF-alpha in the initial host defense against staphylococcal systemic infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-alpha receptor (TNFR1). In this study, we demonstrate that S. aureus, via protein A mediated signaling, induces early shedding of soluble TNFR1 which precedes the secretion of TNF-alpha in vitro and in vivo. The results obtained using a protein A deficient mutant and tnfr1-/- mice strongly suggest that the increased levels of soluble TNFR1 present during S. aureus experimental infection may neutralize circulating TNF-alpha and impair the host inflammatory response. Early shedding of soluble TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response.Fil: Giai, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaFil: Gonzalez, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaFil: Ledo, Camila. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Garofalo, Ailin Natalia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaFil: Gomez, Marisa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; ArgentinaAmerican Society for Microbiology2013-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/mswordapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6594Giai, Constanza; Gonzalez, Cintia Daniela; Ledo, Camila; Garofalo, Ailin Natalia; Di Genaro, Maria Silvia; et al.; Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection; American Society for Microbiology; Infection and Immunity; 81; 11; 11-2013; 4200-42070019-9567enginfo:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/81/11/4200.longinfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00593-13info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:29Zoai:ri.conicet.gov.ar:11336/6594instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:01:29.623CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
title Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
spellingShingle Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
Giai, Constanza
Staphylococcus Aureus
Protein A
Tnf-Alpha
Inflammation
title_short Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
title_full Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
title_fullStr Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
title_full_unstemmed Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
title_sort Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection
dc.creator.none.fl_str_mv Giai, Constanza
Gonzalez, Cintia Daniela
Ledo, Camila
Garofalo, Ailin Natalia
Di Genaro, Maria Silvia
Sordelli, Daniel Oscar
Gomez, Marisa Ines
author Giai, Constanza
author_facet Giai, Constanza
Gonzalez, Cintia Daniela
Ledo, Camila
Garofalo, Ailin Natalia
Di Genaro, Maria Silvia
Sordelli, Daniel Oscar
Gomez, Marisa Ines
author_role author
author2 Gonzalez, Cintia Daniela
Ledo, Camila
Garofalo, Ailin Natalia
Di Genaro, Maria Silvia
Sordelli, Daniel Oscar
Gomez, Marisa Ines
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Staphylococcus Aureus
Protein A
Tnf-Alpha
Inflammation
topic Staphylococcus Aureus
Protein A
Tnf-Alpha
Inflammation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Staphylococcus aureus infections are an important concern in public health due to their increasing incidence and high rates of mortality. The S. aureus success as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of TNF-alpha in the initial host defense against staphylococcal systemic infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-alpha receptor (TNFR1). In this study, we demonstrate that S. aureus, via protein A mediated signaling, induces early shedding of soluble TNFR1 which precedes the secretion of TNF-alpha in vitro and in vivo. The results obtained using a protein A deficient mutant and tnfr1-/- mice strongly suggest that the increased levels of soluble TNFR1 present during S. aureus experimental infection may neutralize circulating TNF-alpha and impair the host inflammatory response. Early shedding of soluble TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response.
Fil: Giai, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Gonzalez, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Ledo, Camila. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina
Fil: Garofalo, Ailin Natalia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina
Fil: Di Genaro, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
Fil: Gomez, Marisa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones En Microbiología y Parasitología Médica; Argentina
description Staphylococcus aureus infections are an important concern in public health due to their increasing incidence and high rates of mortality. The S. aureus success as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of TNF-alpha in the initial host defense against staphylococcal systemic infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients. S. aureus protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-alpha receptor (TNFR1). In this study, we demonstrate that S. aureus, via protein A mediated signaling, induces early shedding of soluble TNFR1 which precedes the secretion of TNF-alpha in vitro and in vivo. The results obtained using a protein A deficient mutant and tnfr1-/- mice strongly suggest that the increased levels of soluble TNFR1 present during S. aureus experimental infection may neutralize circulating TNF-alpha and impair the host inflammatory response. Early shedding of soluble TNFR1 induced by protein A may constitute a novel mechanism by which S. aureus subverts the host immune response.
publishDate 2013
dc.date.none.fl_str_mv 2013-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/6594
Giai, Constanza; Gonzalez, Cintia Daniela; Ledo, Camila; Garofalo, Ailin Natalia; Di Genaro, Maria Silvia; et al.; Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection; American Society for Microbiology; Infection and Immunity; 81; 11; 11-2013; 4200-4207
0019-9567
url http://hdl.handle.net/11336/6594
identifier_str_mv Giai, Constanza; Gonzalez, Cintia Daniela; Ledo, Camila; Garofalo, Ailin Natalia; Di Genaro, Maria Silvia; et al.; Shedding of TNFR1 induced by protein A decreases TNF-alfa; availability and inflammation during systemic Staphylococcus aureus infection; American Society for Microbiology; Infection and Immunity; 81; 11; 11-2013; 4200-4207
0019-9567
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://iai.asm.org/content/81/11/4200.long
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00593-13
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/msword
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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