Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits
| Autor: | Armelle Phalipon, Philippe J. Sansonetti, Khalil A. Kadaoui, Cécile Caubet, Blaise Corthésy, Myriam Tanguy, Séverine Boullier |
|---|---|
| Přispěvatelé: | Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), R&D Laboratory of the Division of Immunology and Allergy [Lausanne, Suisse], Division of Immunology and Allergy [Lausanne, Suisse], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This work was supported by Institut Pasteur and INSERM (to A.P.), by Grants 3200–109545 and 3200–122039 from the Swiss Science Research Foundation (to B.C.), and grants from Région Midi-Pyrénées (no. A2639), Institut National de la Recherche Agronomique and Ministère de l’Agriculture et de la Pêche, Direction Générale de l’Enseignement Supérieur et de la Recherche (to S.B.)., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Chaire Microbiologie et Maladies infectieuses |
| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Immunoglobulin A Cell Membrane Permeability MESH: Ileum / metabolism MESH: Cell Membrane Permeability / immunology MESH: Rabbits medicine.disease_cause Neutralization Shigella flexneri fluids and secretions 0302 clinical medicine Antibody Specificity Immunology and Allergy Shigella Intestinal Mucosa MESH: Lipopolysaccharides / antagonists & inhibitors MESH: Ileum / microbiology 0303 health sciences biology MESH: Dysentery Bacillary / immunology MESH: Inflammation Mediators / antagonists & inhibitors MESH: Dysentery Bacillary / pathology MESH: Shigella flexneri / growth & development MESH: Ileum / pathology MESH: Intestinal Mucosa / immunology Rabbits MESH: Intestinal Mucosa / metabolism Inflammation Mediators medicine.symptom MESH: Shigella flexneri / immunology Immunology Down-Regulation MESH: Intestinal Mucosa / microbiology chemical and pharmacologic phenomena Inflammation MESH: Down-Regulation / immunology digestive system Proinflammatory cytokine Microbiology 03 medical and health sciences Immune system stomatognathic system Ileum medicine Animals Humans MESH: Ileum / immunology MESH: Antibody Specificity Dysentery Bacillary 030304 developmental biology MESH: Intestinal Mucosa / pathology MESH: Humans MESH: Immunoglobulin A Secretory / physiology biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Disease Models Animal MESH: animals MESH: Dysentery Bacillary / prevention & control Immunoglobulin A Secretory biology.protein MESH: Disease Models Animal Bacteria 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, 2009, 183 (9), pp.5879-5885. ⟨10.4049/jimmunol.0901838⟩ Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 183 (9), pp.5879-5885. ⟨10.4049/jimmunol.0901838⟩ |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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-α, IL-6, Cox-2, and IFN-γ, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|