Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis.

Détails

ID Serval
serval:BIB_746D1252CB99
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis.
Périodique
Journal of Immunology
Auteur(s)
Dunne A., Ross P.J., Pospisilova E., Masin J., Meaney A., Sutton C.E., Iwakura Y., Tschopp J., Sebo P., Mills K.H.
ISSN
1550-6606[electronic], 0022-1767[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
185
Numéro
3
Pages
1711-1719
Langue
anglais
Résumé
Inflammasome-mediated IL-1beta production is central to the innate immune defects that give rise to certain autoinflammatory diseases and may also be associated with the generation of IL-17-producing CD4(+) T (Th17) cells that mediate autoimmunity. However, the role of the inflammasome in driving adaptive immunity to infection has not been addressed. In this article, we demonstrate that inflammasome-mediated IL-1beta plays a critical role in promoting Ag-specific Th17 cells and in generating protective immunity against Bordetella pertussis infection. Using a murine respiratory challenge model, we demonstrated that the course of B. pertussis infection was significantly exacerbated in IL-1R type I-defective (IL-1RI(-/-)) mice. We found that adenylate cyclase toxin (CyaA), a key virulence factor secreted by B. pertussis, induced robust IL-1beta production by dendritic cells through activation of caspase-1 and the NALP3-containing inflammasome complex. Using mutant toxins, we demonstrate that CyaA-mediated activation of caspase-1 was not dependent on adenylate cyclase enzyme activity but was dependent on the pore-forming capacity of CyaA. In addition, CyaA promoted the induction of Ag-specific Th17 cells in wild-type but not IL-1RI(-/-) mice. Furthermore, the bacterial load was enhanced in IL-17-defective mice. Our findings demonstrate that CyaA, a virulence factor from B. pertussis, promotes innate IL-1beta production via activation of the NALP3 inflammasome and, thereby, polarizes T cell responses toward the Th17 subtype. In addition to its known role in subverting host immunity, our findings suggest that CyaA can promote IL-1beta-mediated Th17 cells, which promote clearance of the bacteria from the respiratory tract.
Mots-clé
Adenylate Cyclase Toxin/physiology, Adenylate Cyclase Toxin/toxicity, Animals, Bordetella pertussis/immunology, CD4-Positive T-Lymphocytes/enzymology, CD4-Positive T-Lymphocytes/immunology, Carrier Proteins/metabolism, Caspase 1/metabolism, Cell Polarity/immunology, Cells, Cultured, Epitopes, T-Lymphocyte/immunology, Inflammation/enzymology, Inflammation/microbiology, Inflammation Mediators/metabolism, Inflammation Mediators/physiology, Interleukin-17/biosynthesis, Interleukin-17/deficiency, Interleukin-1beta/biosynthesis, Interleukin-1beta/physiology, Intubation, Intratracheal, Mice, Mice, Inbred C57BL, Mice, Knockout, Respiratory Tract Infections/enzymology, Respiratory Tract Infections/microbiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/09/2010 15:20
Dernière modification de la notice
20/08/2019 14:32
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