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
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
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DOI：
10.4049/jimmunol.0903348
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发表时间：
2010-02-15
影响因子：
4.4
通讯作者：
Winter, Nathalie
中科院分区：
文献类型：
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作者：
Martino, Angelo;Badell, Edgar;Winter, Nathalie
对广泛使用的牛分枝杆菌卡介苗（BCG）皮内疫苗的早期免疫应答仍不明确。BCG接种到小鼠耳中后3天，除了中性粒细胞浸润皮肤外，我们还观察到CD 11b（+）Ly-6C（int）Ly-6 G（-）骨髓细胞。神经元耗竭显著增强了它们的募集。这些细胞不同于炎性单核细胞，需要MyD 88依赖的BCG特异性信号侵入皮肤，而中性粒细胞流入是MyD 88独立的。在BCG吞噬作用下，CD 11b（+）Ly-6C（int）Ly-6 G（-）细胞产生NO，这需要IL-1受体。尽管产生NO，但它们不能杀死BCG或非致病性的耻垢分枝杆菌。然而，它们显著损害引流淋巴结中的T细胞引发。通过全反式维甲酸治疗消除它们增加了产生IFN-γ的CD 4 T细胞的数量。因此，卡介苗接种招募先天性骨髓源性抑制细胞，类似于小鼠肿瘤浸润细胞。这些原致病细胞抑制早期T细胞反应，并可能促进BCG的持久性。免疫学杂志，2010，184：2038-2047.
Early immune response to the largely used Mycobactetium bovis bacillus Calmette-Guerin (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. The Journal of Immunology, 2010,184: 2038-2047.