Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA

ABSTRACT Mucosal immunity to the enteric pathogen Shigella flexneri is mediated by secretory IgA (S-IgA) antibodies directed against the O-antigen (O-Ag) side chain of lipopolysaccharide. While secretory antibodies against the O-Ag are known to prevent bacterial invasion of the intestinal epithelium...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stephen J. Forbes, Tia Bumpus, Elizabeth A. McCarthy, Blaise Corthésy, Nicholas J. Mantis
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c55926b829ee43c39ffdcd3a7ede6d6f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c55926b829ee43c39ffdcd3a7ede6d6f
record_format	dspace
spelling	oai:doaj.org-article:c55926b829ee43c39ffdcd3a7ede6d6f2021-11-15T15:38:50ZTransient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA10.1128/mBio.00042-112150-7511https://doaj.org/article/c55926b829ee43c39ffdcd3a7ede6d6f2011-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00042-11https://doaj.org/toc/2150-7511ABSTRACT Mucosal immunity to the enteric pathogen Shigella flexneri is mediated by secretory IgA (S-IgA) antibodies directed against the O-antigen (O-Ag) side chain of lipopolysaccharide. While secretory antibodies against the O-Ag are known to prevent bacterial invasion of the intestinal epithelium, the mechanisms by which this occurs are not fully understood. In this study, we report that the binding of a murine monoclonal IgA (IgAC5) to the O-Ag of S. flexneri serotype 5a suppresses activity of the type 3 secretion (T3S) system, which is necessary for S. flexneri to gain entry into intestinal epithelial cells. IgAC5’s effects on the T3S were rapid (5 to 15 min) and were coincident with a partial reduction in the bacterial membrane potential and a decrease in intracellular ATP levels. Activity of the T3S system returned to normal levels 45 to 90 min following antibody treatment, demonstrating that IgAC5’s effects were transient. Nonetheless, these data suggest a model in which the association of IgA with the O-Ag of S. flexneri partially de-energizes the T3S system and temporarily renders the bacterium incapable of invading intestinal epithelial cells. IMPORTANCE Secretory IgA (S-IgA) serves as the first line of defense against enteric infections. However, despite its well-recognized role in mucosal immunity, relatively little is known at the molecular level about how this class of antibody functions to prevent pathogenic bacteria from penetrating the epithelial barrier. It is generally assumed that S-IgA functions primarily by “immune exclusion,” a phenomenon in which the antibody binds to microbial surface antigens and thereby promotes bacterial agglutination, entrapment in mucus, and physical clearance from the gastrointestinal tract via peristalsis. The results of the present study suggest that in addition to serving as a physical barrier, S-IgA may have a direct impact on the ability of microbial pathogens to secrete virulence factors required for invasion of intestinal epithelial cells.Stephen J. ForbesTia BumpusElizabeth A. McCarthyBlaise CorthésyNicholas J. MantisAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 3 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Stephen J. Forbes Tia Bumpus Elizabeth A. McCarthy Blaise Corthésy Nicholas J. Mantis Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA
description	ABSTRACT Mucosal immunity to the enteric pathogen Shigella flexneri is mediated by secretory IgA (S-IgA) antibodies directed against the O-antigen (O-Ag) side chain of lipopolysaccharide. While secretory antibodies against the O-Ag are known to prevent bacterial invasion of the intestinal epithelium, the mechanisms by which this occurs are not fully understood. In this study, we report that the binding of a murine monoclonal IgA (IgAC5) to the O-Ag of S. flexneri serotype 5a suppresses activity of the type 3 secretion (T3S) system, which is necessary for S. flexneri to gain entry into intestinal epithelial cells. IgAC5’s effects on the T3S were rapid (5 to 15 min) and were coincident with a partial reduction in the bacterial membrane potential and a decrease in intracellular ATP levels. Activity of the T3S system returned to normal levels 45 to 90 min following antibody treatment, demonstrating that IgAC5’s effects were transient. Nonetheless, these data suggest a model in which the association of IgA with the O-Ag of S. flexneri partially de-energizes the T3S system and temporarily renders the bacterium incapable of invading intestinal epithelial cells. IMPORTANCE Secretory IgA (S-IgA) serves as the first line of defense against enteric infections. However, despite its well-recognized role in mucosal immunity, relatively little is known at the molecular level about how this class of antibody functions to prevent pathogenic bacteria from penetrating the epithelial barrier. It is generally assumed that S-IgA functions primarily by “immune exclusion,” a phenomenon in which the antibody binds to microbial surface antigens and thereby promotes bacterial agglutination, entrapment in mucus, and physical clearance from the gastrointestinal tract via peristalsis. The results of the present study suggest that in addition to serving as a physical barrier, S-IgA may have a direct impact on the ability of microbial pathogens to secrete virulence factors required for invasion of intestinal epithelial cells.
format	article
author	Stephen J. Forbes Tia Bumpus Elizabeth A. McCarthy Blaise Corthésy Nicholas J. Mantis
author_facet	Stephen J. Forbes Tia Bumpus Elizabeth A. McCarthy Blaise Corthésy Nicholas J. Mantis
author_sort	Stephen J. Forbes
title	Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA
title_short	Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA
title_full	Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA
title_fullStr	Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA
title_full_unstemmed	Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA
title_sort	transient suppression of <named-content content-type="genus-species">shigella flexneri</named-content> type 3 secretion by a protective o-antigen-specific monoclonal iga
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/c55926b829ee43c39ffdcd3a7ede6d6f
work_keys_str_mv	AT stephenjforbes transientsuppressionofnamedcontentcontenttypegenusspeciesshigellaflexnerinamedcontenttype3secretionbyaprotectiveoantigenspecificmonoclonaliga AT tiabumpus transientsuppressionofnamedcontentcontenttypegenusspeciesshigellaflexnerinamedcontenttype3secretionbyaprotectiveoantigenspecificmonoclonaliga AT elizabethamccarthy transientsuppressionofnamedcontentcontenttypegenusspeciesshigellaflexnerinamedcontenttype3secretionbyaprotectiveoantigenspecificmonoclonaliga AT blaisecorthesy transientsuppressionofnamedcontentcontenttypegenusspeciesshigellaflexnerinamedcontenttype3secretionbyaprotectiveoantigenspecificmonoclonaliga AT nicholasjmantis transientsuppressionofnamedcontentcontenttypegenusspeciesshigellaflexnerinamedcontenttype3secretionbyaprotectiveoantigenspecificmonoclonaliga
_version_	1718427852187107328

Transient Suppression of <named-content content-type="genus-species">Shigella flexneri</named-content> Type 3 Secretion by a Protective O-Antigen-Specific Monoclonal IgA

Ejemplares similares