美国麻省总医院和哈佛医学院Matthias Nahrendorf研究组近日发现，组织特异性巨噬细胞对远端损伤的响应能够影响随后局部免疫应答的结果。这一研究成果于2019年11月12日在线发表在国际学术期刊《免疫》上。

研究人员检测了重要器官中巨噬细胞在这些损伤后对全身反应的贡献。研究人员针对患有心肌梗塞、中风或脓毒症的小鼠的心脏、脑、肝、肾和肺中巨噬细胞数量、来源和基因表达的变化进行了完整统计。主要由局部增殖的加剧推动，组织巨噬细胞数量得以全身性增加。相同器官中的巨噬细胞通过改变组织特异性基因组的表达，对不同的损伤有相似的反应。先出现的心肌梗死由于增强了细菌清除作用从而而提高了随后的肺炎存活率，这是由IFN?活化肺泡巨噬细胞引起的。相反，巨噬细胞中的EGF受体信号转导加剧了炎症性肺损伤。这些数据表明局部损伤可激活远端器官中的巨噬细胞，而靶向巨噬细胞可提高对心肌梗塞、中风和脓毒症后系统并发症的抵抗力。

据悉，心肌梗塞、中风和脓毒症引起全身性炎症和难以处理的机体并发症。

Title: Tissue-Specific Macrophage Responses to Remote Injury Impact the Outcome of Subsequent Local Immune Challenge

Author: Friedrich Felix Hoyer, Kamila Naxerova, Maximilian J. Schloss, Maarten Hulsmans, Anil V. Nair, Partha Dutta, David M. Calcagno, Fanny Herisson, Atsushi Anzai, Yuan Sun, Gregory Wojtkiewicz, David Rohde, Vanessa Frodermann, Katrien Vandoorne, Gabriel Courties, Yoshiko Iwamoto, Christopher S. Garris, David L. Williams, Sylvie Breton, Dennis Brown, Michael Whalen, Peter Libby, Mikael J. Pittet, Kevin R. King, Ralph Weissleder, Filip K. Swirski, Matthias Nahrendorf

Issue&Volume: November 12, 2019

Abstract: Myocardial infarction, stroke, and sepsis trigger systemic inflammation and organism-widecomplications that are difficult to manage. Here, we examined the contribution ofmacrophages residing in vital organs to the systemic response after these injuries.We generated a comprehensive catalog of changes in macrophage number, origin, andgene expression in the heart, brain, liver, kidney, and lung of mice with myocardialinfarction, stroke, or sepsis. Predominantly fueled by heightened local proliferation,tissue macrophage numbers increased systemically. Macrophages in the same organ respondedsimilarly to different injuries by altering expression of tissue-specific gene sets.Preceding myocardial infarction improved survival of subsequent pneumonia due to enhancedbacterial clearance, which was caused by IFN priming of alveolar macrophages. Conversely,EGF receptor signaling in macrophages exacerbated inflammatory lung injury. Our datasuggest that local injury activates macrophages in remote organs and that targetingmacrophages could improve resilience against systemic complications following myocardialinfarction, stroke, and sepsis.

DOI: 10.1016/j.immuni.2019.10.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30454-6