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- Title
Key Role for Respiratory CD103+ Dendritic Cells, IFN-[gamma], and IL-17 in Protection Against Streptococcus pneumoniae Infection in Response to [alpha]-Galactosylceramide.
- Authors
Ivanov, Stoyan; Fontaine, Josette; Paget, Christophe; Macho Fernandez, Elodie; Van Maele, Laurye; Renneson, Joelle; Maillet, Isabelle; Wolf, Natalia Muñoz; Rial, Analia; Léger, Hélène; Ryffel, Bernard; Frisch, Benoit; Chabalgoity, José A; Sirard, Jean Claude; Benecke, Arndt; Faveeuw, Christelle; Trottein, François
- Abstract
Background.Exogenous activation of pulmonary invariant natural killer T (iNKT) cells, a population of lipid-reactive [alpha][beta] 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.
- Publication
Journal of Infectious Diseases, 2012, Vol 206, Issue 5, p723
- ISSN
0022-1899
- Publication type
Journal Article
- DOI
10.1093/infdis/jis413