Mycobacterium bovis Bacillus Calmette-Guerin Vaccination Mobilizes Innate Myeloid-Derived Suppressor Cells Restraining In Vivo T Cell Priming via IL-1R-Dependent Nitric Oxide Production
Résumé
Early immune response to the largely used Mycobacterium bovis bacillusCalmette-Gue´rin (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-6CintLy-6G2 myeloid cells.Neutrophil depletionmarkedly enhanced their recruitment.These cells differed frominflammatory monocytes and required MyD88-dependent BCG-specific signals to invade skin, whereas neutrophil influx was MyD88 independent. Upon BCG phagocytosis, CD11b+Ly-6CintLy-6G2cells produced NO,which required the IL-1 receptor.DespiteNOproduction, theywere unable to killBCGor the nonpathogenicMycobacterium smegmatis.However, theymarkedly impairedTcell priming in the draining lymph node. Their elimination by all-trans retinoid acid treatment increased the number of IFN-g–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.