Transient suppression of Shigella flexneri type 3 secretion by a protective O-antigen-specific monoclonal IgA.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_EE9201EAFE0C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Transient suppression of Shigella flexneri type 3 secretion by a protective O-antigen-specific monoclonal IgA.
Périodique
mBio
Auteur⸱e⸱s
Forbes S.J., Bumpus T., McCarthy E.A., Corthésy B., Mantis N.J.
ISSN
2150-7511
Statut éditorial
Publié
Date de publication
2011
Volume
2
Numéro
3
Pages
e00042-e00011
Langue
anglais
Résumé
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.
Mots-clé
Adenosine Triphosphate/analysis, Animals, Antibodies, Bacterial/immunology, Antibodies, Bacterial/isolation & purification, Antibodies, Monoclonal/immunology, Antibodies, Monoclonal/isolation & purification, Bacterial Proteins/secretion, Cell Membrane/physiology, Cytoplasm/chemistry, Immunoglobulin A/immunology, Immunoglobulin A/isolation & purification, Membrane Potentials, Membrane Transport Proteins/metabolism, Mice, O Antigens/immunology, Shigella flexneri/immunology, Shigella flexneri/metabolism, Time Factors, Virulence Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/12/2011 14:13
Dernière modification de la notice
20/08/2019 16:16
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