title: Mycobacterium bovis bacillus Calmette-Guérin vaccination mobilizes innate myeloid-derived suppressor cells restraining in vivo T cell priming via IL-1R-dependent nitric oxide production.
abstract: Early immune response to the largely used Mycobacterium bovis bacillus Calmette-Guérin (BCG) intradermal vaccine remains ill defined. Three days after BCG inoculation into the mouse ear, in addition to neutrophils infiltrating skin, we observed CD11b(+)Ly-6C(int)Ly-6G(-) myeloid cells. Neutrophil depletion markedly enhanced their recruitment. These cells differed from inflammatory monocytes and required MyD88-dependent BCG-specific signals to invade skin, whereas neutrophil influx was MyD88 independent. Upon BCG phagocytosis, CD11b(+)Ly-6C(int)Ly-6G(-) cells produced NO, which required the IL-1 receptor. Despite NO production, they were unable to kill BCG or the nonpathogenic Mycobacterium smegmatis. However, they markedly impaired T cell priming in the draining lymph node. Their elimination by all-trans retinoid acid treatment increased the number of IFN-gamma-producing CD4 T cells. Thus, BCG vaccination recruits innate myeloid-derived suppressor cells, akin to mouse tumor-infiltrating cells. These propathogenic cells dampen the early T cell response and might facilitate BCG persistence.
authors.affiliation: Institut Pasteur Unité Génétique Mycobactérienne, Université Pierre et Marie Curie-Paris 6, AP-HP Groupe Hospitalier Pitié-Salpétrière Service d'Immunologie, Paris, France.
authors.forename: Angelo
authors.initials: A
authors.lastname: Martino
authors.forename: Edgar
authors.initials: E
authors.lastname: Badell
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Viviane
authors.initials: V
authors.lastname: Balloy
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
authors.forename: Michel-Yves
authors.initials: MY
authors.lastname: Mistou
authors.forename: Béhazine
authors.initials: B
authors.lastname: Combadière
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
chemical_list: D001500:BCG Vaccine; D017472:Receptors, Interleukin-1; D009569:Nitric Oxide