Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Simpson Querrey Lung Institute for Translational Science, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Nat Immunol. 2024 Sep;25(9):1607-1622. doi: 10.1038/s41590-024-01914-w. Epub 2024 Aug 13.
The evolution of T cell molecular signatures in the distal lung of patients with severe pneumonia is understudied. Here, we analyzed T cell subsets in longitudinal bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia, including unvaccinated patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with respiratory failure not linked to pneumonia. In patients with SARS-CoV-2 pneumonia, activation of interferon signaling pathways, low activation of the NF-κB pathway and preferential targeting of spike and nucleocapsid proteins early after intubation were associated with favorable outcomes, whereas loss of interferon signaling, activation of NF-κB-driven programs and specificity for the ORF1ab complex late in disease were associated with mortality. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize individuals who recover, whereas responses against nonstructural proteins and activation of NF-κB are associated with poor outcomes.
T 细胞分子特征在严重肺炎患者远端肺部的演变尚未得到充分研究。在这里，我们分析了 273 例严重肺炎患者的纵向支气管肺泡灌洗液样本中的 T 细胞亚群，其中包括未接种疫苗的感染严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）或与肺炎无关的呼吸衰竭患者。在 SARS-CoV-2 肺炎患者中，干扰素信号通路的激活、NF-κB 通路的低激活以及在插管后早期对刺突蛋白和核衣壳蛋白的优先靶向与良好结局相关，而干扰素信号的丧失、NF-κB 驱动的程序的激活以及 ORF1ab 复合物的特异性与疾病晚期的死亡率相关。这些结果表明，在严重 SARS-CoV-2 肺炎患者中，针对结构 SARS-CoV-2 蛋白的肺泡 T 细胞干扰素反应特征是恢复的个体，而针对非结构蛋白的反应和 NF-κB 的激活与不良结局相关。
