Key role for respiratory CD103(+) dendritic cells, IFN-gamma, and IL-17 in protection against Streptococcus pneumoniae infection in response to alpha-galactosylceramide.
Fiche publication
Date publication
septembre 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FRISCH Benoit
Tous les auteurs :
Ivanov S, Fontaine J, Paget C, Macho Fernandez E, Van Maele L, Renneson J, Maillet I, Wolf NM, Rial A, Leger H, Ryffel B, Frisch B, Chabalgoity JA, Sirard JC, Benecke A, Faveeuw C, Trottein F
Lien Pubmed
Résumé
BACKGROUND: Exogenous activation of pulmonary invariant natural killer T (iNKT) cells, a population of lipid-reactive alphabeta T lymphocytes, with use of mucosal alpha-galactosylceramide (alpha-GalCer) administration, is a promising approach to control respiratory bacterial infections. We undertook the present study to characterize mechanisms leading to alpha-GalCer-mediated protection against lethal infection with Streptococcus pneumoniae serotype 1, a major respiratory pathogen in humans. METHODS AND RESULTS: alpha-GalCer was administered by the intranasal route before infection with S. pneumoniae. We showed that respiratory dendritic cells (DCs), most likely the CD103(+) subset, play a major role in the activation (IFN-gamma and IL-17 release) of pulmonary iNKT cells, whereas alveolar and interstitial macrophages are minor players. After challenge, S. pneumoniae was rapidly (4 hours) eliminated in the alveolar spaces, a phenomenon that depended on respiratory DCs and neutrophils, but not macrophages, and on the early production of both IFN-gamma and IL-17. Protection was also associated with the synthesis of various interferon-dependent and IL-17-associated genes as revealed by transcriptomic analysis. CONCLUSIONS: These data imply a new function for pulmonary CD103(+) DCs in mucosal activation of iNKT cells and establish a critical role for both IFN-gamma and IL-17 signalling pathways in mediating the innate immune response to S. pneumoniae.
Référence
J Infect Dis. 2012 Sep 1;206(5):723-34