Patrolling Alveolar Macrophages Conceal Bacteria from the Immune System to Maintain Homeostasis
Patrolling Alveolar Macrophages Conceal Bacteria from the Immune System to Maintain Homeostasis
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DOI：
10.1016/j.cell.2020.08.020
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发表时间：
2020-10-01
期刊：
影响因子：
64.5
通讯作者：
Kubes, Paul
中科院分区：
文献类型：
--
作者：
Neupane, Arpan Sharma;Willson, Michelle;Kubes, Paul
在呼吸过程中，人类每天吸入超过10,000升的非无菌空气，使一些病原体进入肺泡。有趣的是，肺泡的数量超过了肺泡巨噬细胞 (AM)，这有利于没有 AM 的肺泡。如果AM像大多数组织巨噬细胞一样是固着的，那么这种数量优势就会被病原体利用，除非来自血流的中性粒细胞进行干预。然而，这将转化为无处不在的持续性炎症。对肺泡的体内实时活体成像显示，AM 利用 Kohn 的孔在肺泡内和肺泡之间爬行。重要的是，这些巨噬细胞能够感知、趋化并高效地吞噬吸入的细菌病原体，例如铜绿假单胞菌和金黄色葡萄球菌，从而将细菌与中性粒细胞掩盖起来。损害 AM 对细菌的趋化性会导致多余的中性粒细胞募集，导致不适当的炎症和损伤。在疾病背景下，甲型流感病毒感染通过 II 型干扰素信号通路损害 AM 爬行，这大大增加了继发性细菌合并感染。
During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli revealed AMs crawling in and between alveoli using the pores of Kohn. Importantly, these macrophages sensed, chemotaxed, and, with high efficiency, phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis toward bacteria induced superfluous neutrophil recruitment, leading to inappropriate inflammation and injury. In a disease context, influenza A virus infection impaired AM crawling via the type II interferon signaling pathway, and this greatly increased secondary bacterial co-infection.