Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes
Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes
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DOI：
10.1073/pnas.1905054116
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发表时间：
2019-09-17
影响因子：
11.1
通讯作者：
Clatworthy, Menna R.
中科院分区：
文献类型：
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作者：
Lok, Laurence S. C.;Dennison, Thomas W.;Clatworthy, Menna R.
中性粒细胞在先天免疫中发挥着关键作用。作为占主导地位的循环吞噬细胞，它们会迅速从血流中募集到感染或损伤部位，以内化和消灭微生物。最近，在未感染的器官中发现了中性粒细胞，这挑战了其功能的经典观点。在这里，我们表明中性粒细胞存在于处于稳态的淋巴结（LN）中。使用流式细胞术和共聚焦成像，我们在未受攻击的幼鼠的淋巴结内发现了中性粒细胞，包括引流皮肤、肺部和胃肠道的淋巴结。中性粒细胞在特定的解剖区域（即 T 细胞激活部位）的滤泡间区富集。活体双光子显微镜显示，淋巴结中性粒细胞具有活动性，分别通过高位内皮微静脉和传入淋巴管从血液和组织转运至淋巴结，并与淋巴结中的树突状细胞形成相互作用。与循环中性粒细胞相比，小鼠和人类 LN 中性粒细胞具有不同的表型，具有更高的主要组织相容性复合物 II (MHCII) 表达，表明在 CD4 T 细胞激活中具有潜在作用。在用 IgG 免疫复合物 (IC) 进行离体刺激后，中性粒细胞上调 MHCII 和共刺激分子的表达，并增加 T 细胞活化。在体内，中性粒细胞能够将循环 IC 递送至 LN，这表明其功能范围更广泛。总体而言，我们的数据挑战了中性粒细胞巡逻仅限于稳态循环的看法，将 LN 添加到其常规监视区域。
Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the blood-stream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.