The Secretive Life of Neutrophils Revealed by Intravital Microscopy.
The Secretive Life of Neutrophils Revealed by Intravital Microscopy.
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DOI：
10.3389/fcell.2020.603230
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发表时间：
2020
影响因子：
5.5
通讯作者：
Rankin SM
中科院分区：
文献类型：
--
作者：
De Filippo K;Rankin SM
中性粒细胞是血液中最丰富的循环白细胞，多年来，人们一直认为这些细胞在受到损伤或感染时迅速迁移到组织中，形成宿主防御的第一道防线。虽然之前有文献记载，中性粒细胞游离于肺和肝脏的血管床内，并大量存在于组织的实质中，如脾、淋巴结和骨髓（BM），但这些组织常驻中性粒细胞在稳态下的功能，在对病原体入侵或损伤的反应中，直到最近才被探索。揭示了这些细胞作为免疫调节或免疫辅助的意想不到的作用，并揭示了它们的异质性和可塑性。中性粒细胞是高度运动性的细胞，使用活体显微镜（IVM）在其环境中对细胞进行成像，几乎不需要任何操作，这极大地增加了我们对这些短寿命细胞与其他先天和适应性免疫细胞的功能、迁移行为和相互作用的理解。与先前的教条相反，这些研究表明边缘和组织驻留中性粒细胞是病原体和损伤的第一反应者，在限制感染的传播和随后的免疫反应中起关键作用。中性粒细胞与其他中性粒细胞、白细胞和基质细胞的相互作用也可以调节和调整它们的早期和晚期反应，以根除病原体，最大限度地减少组织损伤，并在某些情况下有助于组织修复。在这篇综述中，我们将跟随中性粒细胞从BM起源到死亡的非凡旅程，探索它们在肺、脾、淋巴结和皮肤中作为组织常驻细胞的作用，并概述中性粒细胞亚群的重要性，它们在稳态下的功能，以及对感染的反应。最后，我们将评论如何在分子水平上更详细地理解这些过程可以导致新疗法的发展。
Neutrophils are the most abundant circulating leukocyte within the blood stream and for many years the dogma has been that these cells migrate rapidly into tissues in response to injury or infection, forming the first line of host defense. While it has previously been documented that neutrophils marginate within the vascular beds of the lung and liver and are present in large numbers within the parenchyma of tissues, such as spleen, lymph nodes, and bone marrow (BM), the function of these tissue resident neutrophils under homeostasis, in response to pathogen invasion or injury has only recently been explored, revealing the unexpected role of these cells as immunoregulators or immune helpers and also unraveling their heterogeneity and plasticity. Neutrophils are highly motile cells and the use of intravital microscopy (IVM) to image cells within their environment with little manipulation has dramatically increased our understanding of the function, migratory behavior, and interaction of these short-lived cells with other innate and adaptive immune cells. Contrary to previous dogma, these studies have shown that marginated and tissue resident neutrophils are the first responders to pathogens and injury, critical in limiting the spread of infection and contributing to the orchestration of the subsequent immune response. The interplay of neutrophils, with other neutrophils, leukocytes, and stroma cells can also modulate and tune their early and late response in order to eradicate pathogens, minimize tissue damage, and, in certain circumstances, contribute to tissue repair. In this review, we will follow the extraordinary journey of neutrophils from their origin in the BM to their death, exploring their role as tissue resident cells in the lung, spleen, lymph nodes, and skin and outlining the importance of neutrophil subsets, their functions under homeostasis, and in response to infection. Finally, we will comment on how understanding these processes in greater detail at a molecular level can lead to development of new therapeutics.