In situ neutrophil efferocytosis shapes T cell immunity to influenza infection.

In situ neutrophil efferocytosis shapes T cell immunity to influenza infection.
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DOI:
10.1038/s41590-020-0746-x
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发表时间:
2020-09
期刊:
影响因子:
30.5
通讯作者:
Kim M
Kim M
中科院分区:
医学1区
文献类型:
--
作者:
Lim K;Kim TH;Trzeciak A;Amitrano AM;Reilly EC;Prizant H;Fowell DJ;Topham DJ;Kim M

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嗜中性粒细胞从血液中早期募集到组织感染部位是先天免疫反应的一个标志。然而,凋亡中性粒细胞在感染组织中清除的机制以及原位efferocytosis的免疫学后果尚不清楚。使用活体多光子显微镜(IV-MPM),我们显示了流感感染小鼠气道内中性粒细胞和组织常驻吞噬细胞之间先前未被识别的相互作用的运动模式。新浸润的炎症单核细胞成为吞噬细胞的主要池,在溶解期对高运动性凋亡中性粒细胞的清除中起关键作用。凋亡中性粒细胞进一步释放表皮生长因子(EGF),促进单核细胞向组织驻留抗原呈递细胞(APCs)分化,激活抗病毒T细胞效应功能。总的来说,这些结果表明,在感染组织中存在中性粒细胞的原位分解对于CD8+ T细胞介导的最佳免疫保护至关重要。
Early recruitment of neutrophils from the blood to sites of tissue infection is a hallmark of innate immune responses. However, little is known about the mechanisms by which apoptotic neutrophils are cleared in infected tissues during resolution and the immunological consequences of in situ efferocytosis. Using intravital multi-photon microscopy (IV-MPM), we show previously unrecognized motility patterns of interactions between neutrophils and tissue-resident phagocytes within the influenza-infected mouse airway. Newly infiltrated inflammatory monocytes become a major pool of phagocytes and play a key role in the clearance of highly motile apoptotic neutrophils during the resolution phase. Apoptotic neutrophils further release epidermal growth factor (EGF) and promote the differentiation of monocytes into tissue-resident antigen-presenting cells (APCs) for activation of anti-viral T cell effector functions. Collectively, these results suggest that the presence of in situ neutrophil resolution at the infected tissue is critical for optimal CD8+ T cell–mediated immune protection.
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