Secretory IgA-mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down-regulating inflammatory circuits.

Détails

ID Serval
serval:BIB_2A3EABD4B57B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Secretory IgA-mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down-regulating inflammatory circuits.
Périodique
Journal of Immunology
Auteur⸱e⸱s
Boullier S., Tanguy M., Kadaoui K.A., Caubet C., Sansonetti P., Corthésy B., Phalipon A.
ISSN
1550-6606[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
183
Numéro
9
Pages
5879-5885
Langue
anglais
Résumé
Shigella, a Gram-negative invasive enteropathogenic bacterium responsible for bacillary dysentery, causes the rupture, invasion, and inflammatory destruction of the human colonic mucosa. We explored the mechanisms of protection mediated by Shigella LPS-specific secretory IgA (SIgA), the major mucosal Ab induced upon natural infection. Bacteria, SIgA, or SIgA-S. flexneri immune complexes were administered into rabbit ligated intestinal loops containing a Peyer's patch. After 8 h, localizations of bacteria, SIgA, and SIgA-S. flexneri immune complexes were examined by immunohistochemistry and confocal microscopy imaging. We found that anti-Shigella LPS SIgA, mainly via immune exclusion, prevented Shigella-induced inflammation responsible for the destruction of the intestinal barrier. Besides this luminal trapping, a small proportion of SIgA-S. flexneri immune complexes were shown to enter the rabbit Peyer's patch and were internalized by dendritic cells of the subepithelial dome region. Local inflammatory status was analyzed by quantitative RT-PCR using newly designed primers for rabbit pro- and anti-inflammatory mediator genes. In Peyer's patches exposed to immune complexes, limited up-regulation of the expression of proinflammatory genes, including TNF-alpha, IL-6, Cox-2, and IFN-gamma, was observed, consistent with preserved morphology. In contrast, in Peyer's patches exposed to Shigella alone, high expression of the same mediators was measured, indicating that neutralizing SIgA dampens the proinflammatory properties of Shigella. These results show that in the form of immune complexes, SIgA guarantees both immune exclusion and neutralization of translocated bacteria, thus preserving the intestinal barrier integrity by preventing bacterial-induced inflammation. These findings add to the multiple facets of the noninflammatory properties of SIgA.
Mots-clé
Immunoglobulin-A, M-Cells, Intercellular Spread, Mucosal Surfaces, Immune-Responses, Dendritic Cells, In-Vivo, Component, Receptor, Bacteria
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/11/2009 16:06
Dernière modification de la notice
20/08/2019 13:09
Données d'usage