Institut Pasteur Unité Génétique Mycobactérienne, Université Pierre et Marie Curie-Paris 6, AP-HP Groupe Hospitalier Pitié-Salpétrière Service d'Immunologie, Paris, France.
J Immunol. 2010 Feb 15;184(4):2038-47. doi: 10.4049/jimmunol.0903348. Epub 2010 Jan 18.
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.
早期对广泛使用的牛分枝杆菌卡介苗（BCG）皮内疫苗的免疫反应仍不清楚。在将 BCG 接种到小鼠耳朵后 3 天，除了浸润皮肤的中性粒细胞外，我们还观察到 CD11b(+)Ly-6C(int)Ly-6G(-)髓样细胞。中性粒细胞耗竭明显增强了它们的募集。这些细胞不同于炎症性单核细胞，需要 MyD88 依赖性 BCG 特异性信号才能侵入皮肤，而中性粒细胞的流入则不依赖于 MyD88。在 BCG 吞噬后，CD11b(+)Ly-6C(int)Ly-6G(-)细胞产生了需要 IL-1 受体的 NO。尽管产生了 NO，但它们无法杀死 BCG 或非致病性的耻垢分枝杆菌。然而，它们显著抑制了引流淋巴结中的 T 细胞启动。用全反式视黄酸处理消除这些细胞可增加 IFN-γ产生的 CD4 T 细胞数量。因此，BCG 疫苗募集先天髓样来源的抑制细胞，类似于小鼠肿瘤浸润细胞。这些促病细胞抑制早期 T 细胞反应，并可能促进 BCG 的持续存在。
