Neutrophils have been reported to acquire surface expression of MHC class II and co-stimulatory molecules as well as T-cell stimulatory activities when cultured with selected cytokines. However, cellular identity of those unusual neutrophils showing antigen presenting cell (APC)-like features still remains elusive. Here we show that both immature and mature neutrophils purified from mouse bone marrow differentiate into a previously unrecognized "hybrid" population showing dual properties of both neutrophils and dendritic cells (DCs) when cultured with granulocyte macrophage-colony-stimulating factor but not with other tested growth factors. The resulting hybrid cells express markers of both neutrophils (Ly6G, CXCR2, and 7/4) and DCs (CD11c, MHC II, CD80, and CD86). They also exhibit several properties typically reserved for DCs, including dendritic morphology, probing motion, podosome formation, production of interleukin-12 and other cytokines, and presentation of various forms of foreign protein antigens to naïve CD4 T cells. Importantly, they retain intrinsic abilities of neutrophils to capture exogenous material, extrude neutrophil extracellular traps, and kill bacteria via cathelicidin production. Not only do our results reinforce the notion that neutrophils can acquire APC-like properties, they also unveil a unique differentiation pathway of neutrophils into neutrophil-DC hybrids that can participate in both innate and adaptive immune responses.

译文

:嗜中性粒细胞据报道在与选定的细胞因子一起培养时会获得II类MHC和共刺激分子的表面表达以及T细胞的刺激活性。但是,那些表现出抗原呈递细胞(APC)样特征的异常嗜中性粒细胞的细胞特性仍然难以捉摸。在这里,我们显示从小鼠骨髓中纯化的未成熟和成熟的嗜中性粒细胞分化为先前无法识别的“杂种”种群,与粒细胞巨噬细胞集落刺激因子一起培养时,嗜中性粒细胞和树突状细胞(DC)具有双重性质,但未与其他测试的嗜中性粒细胞一起培养生长因子。所得的杂交细胞表达中性粒细胞(Ly6G,CXCR2和7/4)和DC(CD11c,MHC II,CD80和CD86)的标志物。它们还表现出通常保留给DC的几种特性,包括树突形态,探测运动,足小体形成,白介素12和其他细胞因子的产生,以及将各种形式的外源蛋白抗原呈递给幼稚的CD4 T细胞。重要的是,它们保留了嗜中性粒细胞捕获外源物质,挤出嗜中性粒细胞胞外捕获物并通过cathelicidin产生杀死细菌的内在能力。我们的结果不仅增强了中性粒细胞可以获得类似APC的特性的观念,而且还揭示了中性粒细胞向中性粒细胞-DC杂交体的独特分化途径,该途径可以参与先天性和适应性免疫应答。

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