Key role for respiratory CD103(+) dendritic cells, IFN-γ, and IL-17 in protection against Streptococcus pneumoniae infection in response to α-galactosylceramide.

Abstract : BACKGROUND: Exogenous activation of pulmonary invariant natural killer T (iNKT) cells, a population of lipid-reactive αβ T lymphocytes, with use of mucosal α-galactosylceramide (α-GalCer) administration, is a promising approach to control respiratory bacterial infections. We undertook the present study to characterize mechanisms leading to α-GalCer-mediated protection against lethal infection with Streptococcus pneumoniae serotype 1, a major respiratory pathogen in humans. METHODS AND RESULTS: α-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-γ 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-γ 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-γ and IL-17 signalling pathways in mediating the innate immune response to S. pneumoniae.
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Journal of Infectious Diseases, Oxford University Press (OUP), 2012, 206 (5), pp.723-34. 〈10.1093/infdis/jis413〉
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http://www.hal.inserm.fr/inserm-00926616
Contributeur : Jean-Claude Sirard <>
Soumis le : jeudi 9 janvier 2014 - 21:58:54
Dernière modification le : mardi 3 juillet 2018 - 11:45:38

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Stoyan Ivanov, Josette Fontaine, Christophe Paget, Elodie Macho Fernandez, Laurye Van Maele, et al.. Key role for respiratory CD103(+) dendritic cells, IFN-γ, and IL-17 in protection against Streptococcus pneumoniae infection in response to α-galactosylceramide.. Journal of Infectious Diseases, Oxford University Press (OUP), 2012, 206 (5), pp.723-34. 〈10.1093/infdis/jis413〉. 〈inserm-00926616〉

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