Mechanisms of Invariant NKT Cell Activity in Restraining Bacillus anthracis Systemic Dissemination.
Exogenous activation of invariant NKT (iNKT) cells by the superagonist α-galactosylceramide (α-GalCer) can protect against cancer, autoimmune diseases, and infections. In the current study, we investigated the effect of α-GalCer against Bacillus anthracis infection, the agent of anthrax. Using an experimental model of s.c. B. anthracis infection (an encapsulated nontoxigenic strain), we show that concomitant administration of α-GalCer delayed B. anthracis systemic dissemination and prolonged mouse survival. Depletion of subcapsular sinus CD169-positive macrophages by clodronate-containing liposome was associated with a lack of iNKT cell activation in the draining lymph nodes (dLNs) and prevented the protective effect of α-GalCer on bacterial dissemination out of the dLNs. Production of IFN-γ triggered chemokine (C-C motif) ligand 3 synthesis and recruitment of neutrophils in the dLNs, leading to the restraint of B. anthracis dissemination. Our data highlight a novel immunological pathway leading to the control of B. anthracis infection, a finding that might lead to improved therapeutics based on iNKT cells.
Pathogénie des Toxi-Infections Bactériennes, Département de Microbiologie, Institut Pasteur, 75724 Paris, France; mathieu.legars1@gmail.com.
Mathieu
M
Le Gars
Pathogénie des Toxi-Infections Bactériennes, Département de Microbiologie, Institut Pasteur, 75724 Paris, France.
Michel
M
Haustant
Pathogénie des Toxi-Infections Bactériennes, Département de Microbiologie, Institut Pasteur, 75724 Paris, France.
Maria
M
Klezovich-Bénard
Centre d'Infection et d'Immunité de Lille, INSERM U1019, CNRS UMR 8204, Universitaire de Lille, Centre Hospitalier Régional Universitaire de Lille-Institut Pasteur de Lille, 59000 Lille, France.
Christophe
0000-0002-5374-5407
C
Paget
Centre d'Infection et d'Immunité de Lille, INSERM U1019, CNRS UMR 8204, Universitaire de Lille, Centre Hospitalier Régional Universitaire de Lille-Institut Pasteur de Lille, 59000 Lille, France.
François
0000-0003-3373-1814
F
Trottein
Pathogénie des Toxi-Infections Bactériennes, Département de Microbiologie, Institut Pasteur, 75724 Paris, France.
Pierre L
PL
Goossens
Pathogénie des Toxi-Infections Bactériennes, Département de Microbiologie, Institut Pasteur, 75724 Paris, France.|Unité Interactions Hôte-Agents Pathogènes, Institut de Recherche Biomédicale des Armées, 91223 Brétigny-sur-Orge, France; and.|Ecole du Val-de-Grâce, 75005 Paris, France.
Jean-Nicolas
JN
Tournier
D000818:Animals; D000881:Anthrax / Q000276:immunology* / Q000382:microbiology* / Q000628:therapy; D001408:Bacillus anthracis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*