小柯机器人

2021年1月11日，《自然》杂志在线发表了美国西北大学Richard G. Wunderink等研究人员的合作成果。该研究揭示出SARS-CoV-2肺炎中巨噬细胞和T细胞之间的回路。

研究人员收集了88例SARS-CoV-2引起的呼吸衰竭患者和211例其他病原体已知或疑似肺炎患者的支气管肺泡灌洗液样本，并对其进行了流式细胞术和大量转录组分析。研究人员在插管后48小时内对10例严重COVID-19患者收集的10个支气管肺泡灌洗液样品进行了单细胞RNA测序。在大多数SARS-CoV-2感染患者中，肺泡空间持续富含T细胞和单核细胞。

大量和单细胞转录组谱分析表明，SARS-CoV-2感染了肺泡巨噬细胞，而巨噬细胞反过来又通过产生T细胞趋化因子做出反应。这些T细胞产生γ-干扰素以诱导肺泡巨噬细胞释放炎性细胞因子，并进一步促进T细胞活化。总的来说，这些结果表明SARS-CoV-2可引起缓慢进展、空间限制的肺泡炎，其中携带SARS-CoV-2的肺泡巨噬细胞和T细胞形成正反馈回路，从而驱动持续的肺泡炎症。

据介绍，一些感染了SARS-CoV-2的患者会出现严重的肺炎和急性呼吸窘迫综合症（ARDS）。这些患者的明显临床特征导致人们推测，SARS-CoV-2感染的肺泡对病毒的免疫反应与其他类型的肺炎不同。

附：英文原文

Title: Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia

Author: Rogan A. Grant, Luisa Morales-Nebreda, Nikolay S. Markov, Suchitra Swaminathan, Melissa Querrey, Estefany R. Guzman, Darryl A. Abbott, Helen K. Donnelly, Alvaro Donayre, Isaac A. Goldberg, Zasu M. Klug, Nicole Borkowski, Ziyan Lu, Hermon Kihshen, Yuliya Politanska, Lango Sichizya, Mengjia Kang, Ali Shilatifard, Chao Qi, Jon W. Lomasney, A. Christine Argento, Jacqueline M. Kruser, Elizabeth S. Malsin, Chiagozie O. Pickens, Sean B. Smith, James M. Walter, Anna E. Pawlowski, Daniel Schneider, Prasanth Nannapaneni, Hiam Abdala-Valencia, Ankit Bharat, Cara J. Gottardi, G. R. Scott Budinger, Alexander V. Misharin, Benjamin D. Singer, Richard G. Wunderink

Issue&Volume: 2021-01-11

Abstract: Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS)1. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia2. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA-seq on 10 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.

DOI: 10.1038/s41586-020-03148-w

Source: https://www.nature.com/articles/s41586-020-03148-w

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html