Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity

Autores
Nempont, Clément; Cayet, Delphine; Rumbo, Martín; Bompard, Coralie; Villeret, Vincent; Sirard, Jean-Claude
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
TLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs). Flagellin is a unique MAMP because it harbors 1) an antigenic hypervariable region and 2) a conserved domain involved in TLR5-dependent systemic and mucosal proinflammatory and adjuvant activities. In this study, the contribution of the flagellin domains in TLR5 activation was investigated. We showed that TLR5 signaling can be neutralized in vivo by flagellin-specific Abs, which target the conserved domain. However, deletions of flagellin's hypervariable region abrogated the protein's intrinsic ability to trigger the production of neutralizing Abs. The fact that MAMP-specific Abs block TLR-mediated responses shows that this type of neutralization is a novel mechanism for down-regulating innate immunity. The stimulation of mucosal innate immunity and adjuvancy to foreign Ag was not altered by the hypervariable domain deletions. In contrast, this domain is essential to trigger systemic innate immunity, suggesting that there are distinct mechanisms for TLR5 activation in systemic and mucosal compartments. In summary, specific MAMP determinants control the production of neutralizing Abs and the compartmentalization of innate responses.
Laboratorio de Investigaciones del Sistema Inmune
Materia
Biología
TLR-5
Inmunología
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/84107

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repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunityNempont, ClémentCayet, DelphineRumbo, MartínBompard, CoralieVilleret, VincentSirard, Jean-ClaudeBiologíaTLR-5InmunologíaTLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs). Flagellin is a unique MAMP because it harbors 1) an antigenic hypervariable region and 2) a conserved domain involved in TLR5-dependent systemic and mucosal proinflammatory and adjuvant activities. In this study, the contribution of the flagellin domains in TLR5 activation was investigated. We showed that TLR5 signaling can be neutralized in vivo by flagellin-specific Abs, which target the conserved domain. However, deletions of flagellin's hypervariable region abrogated the protein's intrinsic ability to trigger the production of neutralizing Abs. The fact that MAMP-specific Abs block TLR-mediated responses shows that this type of neutralization is a novel mechanism for down-regulating innate immunity. The stimulation of mucosal innate immunity and adjuvancy to foreign Ag was not altered by the hypervariable domain deletions. In contrast, this domain is essential to trigger systemic innate immunity, suggesting that there are distinct mechanisms for TLR5 activation in systemic and mucosal compartments. In summary, specific MAMP determinants control the production of neutralizing Abs and the compartmentalization of innate responses.Laboratorio de Investigaciones del Sistema Inmune2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf2036-2043http://sedici.unlp.edu.ar/handle/10915/84107enginfo:eu-repo/semantics/altIdentifier/issn/0022-1767info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.181.3.2036info: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:UNLP2025-09-29T11:16:11Zoai:sedici.unlp.edu.ar:10915/84107Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:11.445SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
title Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
spellingShingle Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
Nempont, Clément
Biología
TLR-5
Inmunología
title_short Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
title_full Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
title_fullStr Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
title_full_unstemmed Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
title_sort Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
dc.creator.none.fl_str_mv Nempont, Clément
Cayet, Delphine
Rumbo, Martín
Bompard, Coralie
Villeret, Vincent
Sirard, Jean-Claude
author Nempont, Clément
author_facet Nempont, Clément
Cayet, Delphine
Rumbo, Martín
Bompard, Coralie
Villeret, Vincent
Sirard, Jean-Claude
author_role author
author2 Cayet, Delphine
Rumbo, Martín
Bompard, Coralie
Villeret, Vincent
Sirard, Jean-Claude
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Biología
TLR-5
Inmunología
topic Biología
TLR-5
Inmunología
dc.description.none.fl_txt_mv TLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs). Flagellin is a unique MAMP because it harbors 1) an antigenic hypervariable region and 2) a conserved domain involved in TLR5-dependent systemic and mucosal proinflammatory and adjuvant activities. In this study, the contribution of the flagellin domains in TLR5 activation was investigated. We showed that TLR5 signaling can be neutralized in vivo by flagellin-specific Abs, which target the conserved domain. However, deletions of flagellin's hypervariable region abrogated the protein's intrinsic ability to trigger the production of neutralizing Abs. The fact that MAMP-specific Abs block TLR-mediated responses shows that this type of neutralization is a novel mechanism for down-regulating innate immunity. The stimulation of mucosal innate immunity and adjuvancy to foreign Ag was not altered by the hypervariable domain deletions. In contrast, this domain is essential to trigger systemic innate immunity, suggesting that there are distinct mechanisms for TLR5 activation in systemic and mucosal compartments. In summary, specific MAMP determinants control the production of neutralizing Abs and the compartmentalization of innate responses.
Laboratorio de Investigaciones del Sistema Inmune
description TLRs trigger immunity by detecting microbe-associated molecular patterns (MAMPs). Flagellin is a unique MAMP because it harbors 1) an antigenic hypervariable region and 2) a conserved domain involved in TLR5-dependent systemic and mucosal proinflammatory and adjuvant activities. In this study, the contribution of the flagellin domains in TLR5 activation was investigated. We showed that TLR5 signaling can be neutralized in vivo by flagellin-specific Abs, which target the conserved domain. However, deletions of flagellin's hypervariable region abrogated the protein's intrinsic ability to trigger the production of neutralizing Abs. The fact that MAMP-specific Abs block TLR-mediated responses shows that this type of neutralization is a novel mechanism for down-regulating innate immunity. The stimulation of mucosal innate immunity and adjuvancy to foreign Ag was not altered by the hypervariable domain deletions. In contrast, this domain is essential to trigger systemic innate immunity, suggesting that there are distinct mechanisms for TLR5 activation in systemic and mucosal compartments. In summary, specific MAMP determinants control the production of neutralizing Abs and the compartmentalization of innate responses.
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/10915/84107
url http://sedici.unlp.edu.ar/handle/10915/84107
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0022-1767
info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.181.3.2036
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
2036-2043
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution 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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