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


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.
Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, France.
Stoyan
S
Ivanov
Josette
J
Fontaine
Christophe
C
Paget
Elodie
E
Macho Fernandez
Laurye
L
Van Maele
Joelle
J
Renneson
Isabelle
I
Maillet
Natalia Muñoz
NM
Wolf
Analia
A
Rial
Hélène
H
Léger
Bernard
B
Ryffel
Benoit
B
Frisch
José A
JA
Chabalgoity
Jean Claude
JC
Sirard
Arndt
A
Benecke
Christelle
C
Faveeuw
François
F
Trottein
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005699:Galactosylceramides / Q000494:pharmacology* / Q000627:therapeutic use; D007113:Immunity, Innate / Q000276:immunology; D039001:Integrin alpha Chains / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology*
D015703:Antigens, CD; D005699:Galactosylceramides; D039001:Integrin alpha Chains; D020381:Interleukin-17; C091367:alpha E integrins; C493154:alpha-galactosylceramide; D007371:Interferon-gamma