Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses

Certain bacteria use a type III secretion system (TTSS) to deliver effector proteins that interfere with cell function into host cells. While transcription of genes encoding TTSS components has been demonstrated, studies to date have failed to identify TTSS effector proteins in Bordetella pertussis....

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Detalles Bibliográficos
Autores: Fennelly, Neil K., Sisti, Federico, Higgins, Sarah C., Ross, Pádraig J., Van Der Heide, Han, Mooi, Frits R., Boyd, Aoife, Mills, Kingston H. G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:Argentina
Institución:Universidad Nacional de La Plata
Repositorio:SEDICI (UNLP)
Idioma:inglés
OAI Identifier:oai:sedici.unlp.edu.ar:10915/83054
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83054
Access Level:acceso abierto
Palabra clave:Ciencias Exactas
Bordetella pertussis
Enfermedades del Sistema Inmune
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spelling Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responsesFennelly, Neil K.Sisti, FedericoHiggins, Sarah C.Ross, Pádraig J.Van Der Heide, HanMooi, Frits R.Boyd, AoifeMills, Kingston H. G.Ciencias ExactasBordetella pertussisEnfermedades del Sistema InmuneCertain bacteria use a type III secretion system (TTSS) to deliver effector proteins that interfere with cell function into host cells. While transcription of genes encoding TTSS components has been demonstrated, studies to date have failed to identify TTSS effector proteins in Bordetella pertussis. Here we present the first evidence of a functionally active TTSS in B. pertussis. Three known TTSS effectors, Bsp22, BopN, and BopD, were identified as TTSS substrates in B. pertussis 12743. We found expression of Bsp22 in a significant proportion of clinical isolates but not in common laboratory-adapted strains of B. pertussis. We generated a TTSS mutant of B. pertussis 12743 and showed that it induced significantly lower respiratory tract colonization in mice than the wild-type bacteria. Respiratory infection of mice with the mutant bacteria induced significantly greater innate proinflammatory cytokine production in the lungs soon after challenge, and this correlated with significantly higher antigen-specific interleukin-17, gamma interferon, and immunoglobulin G responses later in infection. Our findings suggest that the TTSS subverts innate and adaptive immune responses during infection of the lungs and may be a functionally important virulence factor for B. pertussis infection of humans.Instituto de Biotecnologia y Biologia Molecular2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf1257-1266http://sedici.unlp.edu.ar/handle/10915/83054enginfo:eu-repo/semantics/altIdentifier/issn/0019-9567info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00836-07info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2024-05-08T12:53:43Zoai:sedici.unlp.edu.ar:10915/83054Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292024-05-08 12:53:44.067SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
title Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
spellingShingle Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
Fennelly, Neil K.
Ciencias Exactas
Bordetella pertussis
Enfermedades del Sistema Inmune
title_short Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
title_full Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
title_fullStr Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
title_full_unstemmed Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
title_sort Bordetella pertussis expresses a functional type III secretion system that subverts protective innate and adaptive immune responses
dc.creator.none.fl_str_mv Fennelly, Neil K.
Sisti, Federico
Higgins, Sarah C.
Ross, Pádraig J.
Van Der Heide, Han
Mooi, Frits R.
Boyd, Aoife
Mills, Kingston H. G.
author Fennelly, Neil K.
author_facet Fennelly, Neil K.
Sisti, Federico
Higgins, Sarah C.
Ross, Pádraig J.
Van Der Heide, Han
Mooi, Frits R.
Boyd, Aoife
Mills, Kingston H. G.
author_role author
author2 Sisti, Federico
Higgins, Sarah C.
Ross, Pádraig J.
Van Der Heide, Han
Mooi, Frits R.
Boyd, Aoife
Mills, Kingston H. G.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Bordetella pertussis
Enfermedades del Sistema Inmune
topic Ciencias Exactas
Bordetella pertussis
Enfermedades del Sistema Inmune
description Certain bacteria use a type III secretion system (TTSS) to deliver effector proteins that interfere with cell function into host cells. While transcription of genes encoding TTSS components has been demonstrated, studies to date have failed to identify TTSS effector proteins in Bordetella pertussis. Here we present the first evidence of a functionally active TTSS in B. pertussis. Three known TTSS effectors, Bsp22, BopN, and BopD, were identified as TTSS substrates in B. pertussis 12743. We found expression of Bsp22 in a significant proportion of clinical isolates but not in common laboratory-adapted strains of B. pertussis. We generated a TTSS mutant of B. pertussis 12743 and showed that it induced significantly lower respiratory tract colonization in mice than the wild-type bacteria. Respiratory infection of mice with the mutant bacteria induced significantly greater innate proinflammatory cytokine production in the lungs soon after challenge, and this correlated with significantly higher antigen-specific interleukin-17, gamma interferon, and immunoglobulin G responses later in infection. Our findings suggest that the TTSS subverts innate and adaptive immune responses during infection of the lungs and may be a functionally important virulence factor for B. pertussis infection of humans.
publishDate 2008
dc.date.none.fl_str_mv 2008
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/83054
url http://sedici.unlp.edu.ar/handle/10915/83054
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0019-9567
info:eu-repo/semantics/altIdentifier/doi/10.1128/IAI.00836-07
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
1257-1266
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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