De Filippo Katia, Rankin Sara M
Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Front Cell Dev Biol. 2020 Nov 10;8:603230. doi: 10.3389/fcell.2020.603230. eCollection 2020.
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.
中性粒细胞是血流中最丰富的循环白细胞，多年来一直存在的观点是，这些细胞会在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。虽然此前已有文献记载中性粒细胞在肺和肝的血管床中边缘化，并大量存在于脾脏、淋巴结和骨髓等组织实质中，但这些组织驻留中性粒细胞在稳态下、对病原体入侵或损伤的反应中的功能直到最近才被探索，揭示了这些细胞作为免疫调节因子或免疫辅助细胞的意外作用，同时也揭示了它们的异质性和可塑性。中性粒细胞是高度移动的细胞，利用活体显微镜（IVM）在几乎不进行操作的情况下对其所处环境中的细胞进行成像，极大地增进了我们对这些短命细胞的功能、迁移行为以及它们与其他固有免疫和适应性免疫细胞相互作用的理解。与之前的观点相反，这些研究表明，边缘化的和组织驻留的中性粒细胞是对病原体和损伤的第一反应者，在限制感染扩散和促进后续免疫反应的协调方面至关重要。中性粒细胞与其他中性粒细胞、白细胞和基质细胞之间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、将组织损伤降至最低，并且在某些情况下有助于组织修复。在这篇综述中，我们将追踪中性粒细胞从骨髓起源到死亡的非凡历程，探讨它们作为肺、脾脏、淋巴结和皮肤中组织驻留细胞的作用，并概述中性粒细胞亚群的重要性、它们在稳态下以及对感染反应中的功能。最后，我们将评论在分子水平上更详细地理解这些过程如何能够促成新疗法的开发。
