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

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 c...

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Autores principales: Nempont, Clément, Cayet, Delphine, Rumbo, Martín, Bompard, Coralie, Villeret, Vincent, Sirard, Jean-Claude
Formato: Articulo
Lenguaje:Inglés
Publicado: 2008
Materias:
Biología
TLR-5
Inmunología
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84107
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84107
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
TLR-5
Inmunología
spellingShingle Biología
TLR-5
Inmunología
Nempont, Clément
Cayet, Delphine
Rumbo, Martín
Bompard, Coralie
Villeret, Vincent
Sirard, Jean-Claude
Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
topic_facet Biología
TLR-5
Inmunología
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.
format Articulo
Articulo
author Nempont, Clément
Cayet, Delphine
Rumbo, Martín
Bompard, Coralie
Villeret, Vincent
Sirard, Jean-Claude
author_facet Nempont, Clément
Cayet, Delphine
Rumbo, Martín
Bompard, Coralie
Villeret, Vincent
Sirard, Jean-Claude
author_sort Nempont, Clément
title Deletion of Flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity
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
publishDate 2008
url http://sedici.unlp.edu.ar/handle/10915/84107
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