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Build a single-cell immune map of COVID-19 pneumonia
Build a single-cell immune map of COVID-19 pneumonia. Cell Research | Qian Junbin’s team builds a single-cell immune map of COVID-19 pneumonia and reveals the mechanism of severe disease.
In 2020, the new coronavirus rages around the world, posing a huge threat to human life and health, and it also brings immeasurable losses to social and economic operations.
Although most people infected with the COVID-19 pneumonia virus are asymptomatic or have only mild to moderate symptoms, about 20% of infected people will worsen the symptoms of pneumonia, and about 5% of patients will develop acute respiratory distress syndrome. Facing death. So what is the difference in the pathogenic mechanism between COVID-19 pneumonia and ordinary pneumonia, and what factors determine whether patients with COVID-19 disease will turn from mild to severe?
Recently, researcher Qian Junbin’s research team from the Obstetrics and Gynecology Hospital of Zhejiang University School of Medicine, Professor Diether Lambrechts of the VIB Institute of Belgium and Leuven University and other teams jointly published an online publication entitled “Discriminating mild from critical COVID-19 by” in Cell Research. innate and adaptive immune single-cell profiling of bronchoalveolar lavages”.
The study performed single-cell transcriptome and immune group (TCR, BCR) combined sequencing on the alveolar lavage fluid of 22 patients with COVID-19 pneumonia and 13 patients with common pneumonia, and systematically constructed an immune response map of COVID-19 pneumonia, the first time in single-cell The difference between the pathogenic mechanism of COVID-19 pneumonia and ordinary pneumonia is compared at the level, and the key immunological dynamic mechanism of mild to severe COVID-19 pneumonia is revealed after integrated analysis.
The study found that the microenvironment of the alveolar lavage fluid of patients with COVID-19 disease has significant cell composition changes, including a large number of activated neutrophils, monocytes, B cells, NK cells, etc., but alveolar macrophages, epithelial cells, etc. However, cell types are significantly reduced. After in-depth cluster analysis of each cell type, the study defined a single-cell map of pneumonia alveolar lavage fluid composed of up to 50 cell phenotypes.
Subsequent trajectory analysis found significant differences in the differentiation of multiple immune cell types. For example, patients with moderate and mild cases of COVID-19 disease have more differentiation of CD8+TRM cells and CD4+ TH17 cells than severe cases, of which the former has obvious TCR clonal proliferation; while in severe patients, a large number of CD8+ TEX and CD4+ TH1 cells that promote inflammation have emerged. , The latter has seen a substantial increase in TCR clones.
In addition, the plasma cell BCR clones of patients with COVID-19 have increased significantly, but they will soon enter the terminal stage of dysfunction. The study also found that monocytes in critically ill patients have a strong inflammatory phenotype, but their ability to differentiate into macrophages is impaired, so that they lack alveolar macrophages to clean up virus-infected cells.
The study further analyzed the expression of virus-specific genes from single-cell transcriptome data, and found that the new coronavirus gene is not only expressed in infected epithelial cells, but also in a variety of immune cells. What’s more interesting is that the 11 major genes of the new coronavirus show differential expression. For example, the S gene is mainly expressed in epithelial cells, while N and ORF10 are more abundant in immune cells.
Further analysis revealed that the epithelial cells expressing the S gene exhibited immune escape phenomena that enhanced virus replication and proliferation, while the neutrophils expressing the N gene exhibited significant innate immune activation, suggesting that the neutrophils are actively cleaning the virus. Play an important role. However, such neutrophils express a large number of inflammatory cytokines at the same time and exhibit a long-term uncontrolled activation state, which may be the main culprit leading to cytokine storm and severe disease.
Finally, the study analyzed the feasibility of using a variety of pathological cell phenotypes as therapeutic targets, and discussed the potential mechanism of current use of hormone therapy such as dexamethasone in the treatment of severe COVID-19 pneumonia, in order to develop new fights against the new coronavirus and rescue severe cases. The patient approach provides important theoretical support.
(source:internet, reference only)