小柯机器人

法国南特大学Karim Asehnoune、Jeremie Poschmann、Antoine Roquilly和澳大利亚墨尔本大学Jose A. Villadangos课题组合作，最新研究发现炎症消退后肺泡巨噬细胞发生表观遗传改变造成肺部长期免疫瘫痪。2020年5月18日出版的《自然-免疫学》发表了这项成果

败血症和外伤会导致炎症和医院获得性肺炎的易感性增加。由于巨噬细胞的吞噬作用在细菌控制过程中起至关重要的作用，因此研究人员探究了炎症消退后巨噬细胞的吞噬活性。

原发性肺炎消退数周后，鼠肺泡巨噬细胞（AMs）仍表现出吞噬能力差。这些瘫痪的AM是从发生了致免疫耐受性表观遗传学改变的驻留AM演变而来。这种适应不是由病原体的直接接触引起的，而是由原发性感染消退后局部建立的继发性免疫抑制信号诱导的。

信号调节蛋白α（SIRPα）在诱导致免疫耐受性微环境的建立中起着关键作用。在患有全身性炎症的病人中，AM和循环单核细胞仍显示出与炎症消退六个月后一致的重编程改变。对SIRPα的抗体阻断可恢复重症患者单核细胞的吞噬功能，这为预防医院获得性肺炎提供了潜在策略。

附：英文原文

Title: Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis

Author: Antoine Roquilly, Cedric Jacqueline, Marion Davieau, Alice Moll, Abderrahmane Sadek, Cynthia Fourgeux, Paul Rooze, Alexis Broquet, Barbara Misme-Aucouturier, Tanguy Chaumette, Mickael Vourch, Raphael Cinotti, Nadege Marec, Vanessa Gauttier, Hamish E. G. McWilliam, Frederic Altare, Jeremie Poschmann, Jose A. Villadangos, Karim Asehnoune

Issue&Volume: 2020-05-18

Abstract: Sepsis and trauma cause inflammation and elevated susceptibility to hospital-acquired pneumonia. As phagocytosis by macrophages plays a critical role in the control of bacteria, we investigated the phagocytic activity of macrophages after resolution of inflammation. After resolution of primary pneumonia, murine alveolar macrophages (AMs) exhibited poor phagocytic capacity for several weeks. These paralyzed AMs developed from resident AMs that underwent an epigenetic program of tolerogenic training. Such adaptation was not induced by direct encounter of the pathogen but by secondary immunosuppressive signals established locally upon resolution of primary infection. Signal-regulatory protein α (SIRPα) played a critical role in the establishment of the microenvironment that induced tolerogenic training. In humans with systemic inflammation, AMs and also circulating monocytes still displayed alterations consistent with reprogramming six months after resolution of inflammation. Antibody blockade of SIRPα restored phagocytosis in monocytes of critically ill patients in vitro, which suggests a potential strategy to prevent hospital-acquired pneumonia.

DOI: 10.1038/s41590-020-0673-x

Source: https://www.nature.com/articles/s41590-020-0673-x

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex