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.
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.
Martino
Angelo
A
Institut Pasteur Unité Génétique Mycobactérienne, Université Pierre et Marie Curie-Paris 6, AP-HP Groupe Hospitalier Pitié-Salpétrière Service d'Immunologie, Paris, France.
Badell
Edgar
E
Abadie
Valérie
V
Balloy
Viviane
V
Chignard
Michel
M
Mistou
Michel-Yves
MY
Combadière
Béhazine
B
Combadière
Christophe
C
Winter
Nathalie
N
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
D001500:BCG Vaccine; D017472:Receptors, Interleukin-1; D009569:Nitric Oxide