M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.
M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.
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DOI：
10.1172/jci.insight.91868
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发表时间：
2017-04-06
期刊：
影响因子：
8
通讯作者：
Ho LP
中科院分区：
文献类型：
--
作者：
Cole SL;Dunning J;Kok WL;Benam KH;Benlahrech A;Repapi E;Martinez FO;Drumright L;Powell TJ;Bennett M;Elderfield R;Thomas C;MOSAIC investigators;Dong T;McCauley J;Liew FY;Taylor S;Zambon M;Barclay W;Cerundolo V;Openshaw PJ;McMichael AJ;Ho LP
在每个流感季节，一群不同的年轻、健康、没有危险因素的人会死于危及生命的感染。为了更好地了解这一原因，我们分析了一组独特的患者的血液中广泛的免疫反应，这些患者包括在一个流感季节因呼吸衰竭而住院和没有呼吸衰竭的先前健康的人，以及感染一种特定的甲型流感病毒株。这一分析与具有已知危险因素的类似住院的流感患者(总共招募了60名患者)进行了比较。我们发现，在这些先前健康的严重疾病患者中，促炎症单核细胞的特定亚群持续增加，具有高肿瘤坏死因子-α表达和类似M1的表型(与病毒滴度无关)。用小鼠流感模型加强了类M1单核细胞与免疫病理学的关系，在不同模型(包括高致病性H5N1毒株)产生的严重感染中，循环中类M1单核细胞水平也很高。此外，观察到肺中M1/M2巨噬细胞比率升高。这些研究确定了一种特定的单核细胞亚型，作为这一亚组重病患者的疾病严重程度的可改变的免疫决定因素，提供了潜在的新的治疗途径。在一组流感患者中，以前健康的和年轻的死于危及生命的疾病的患者被定义为单核细胞循环中高水平的m1样肿瘤坏死因子-α。
In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of n = 60 patients recruited). We found a sustained increase in a specific subset of proinflammatory monocytes, with high TNF-α expression and an M1-like phenotype (independent of viral titers), in these previously healthy patients with severe disease. The relationship between M1-like monocytes and immunopathology was strengthened using murine models of influenza, in which severe infection generated using different models (including the high-pathogenicity H5N1 strain) was also accompanied by high levels of circulating M1-like monocytes. Additionally, a raised M1/M2 macrophage ratio in the lungs was observed. These studies identify a specific subtype of monocytes as a modifiable immunological determinant of disease severity in this subgroup of severely ill, previously healthy patients, offering potential novel therapeutic avenues. In a cohort of influenza patients, previously healthy and young patients who succumbed to life-threatening disease were defined by high levels of circulating M1-like, TNF-αhi monocytes.