Single-celled RNA sequencing reveals a dynamic immunological landscape during the early stages of bubonic plague


This study is led by Dr. Ruifu Yang, Dr. Zongmin Du (State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology) and Dr. Fan Pei (Centre for Pioneering Innovation in Biomedicine, School of Life Sciences, Peking University).

Yersinia pestis (Y. pestis), the causative agent of plague, caused the death of millions of people in three epidemics worldwide in history. Plague is mostly a zoonotic disease transmitted by fleas. While outbreaks of human plague only sporadically occur worldwide each year, the threat of plague to humans and society should not be underestimated. Three subtypes of the disease are commonly found in clinic, namely bubonic plague, septicemia, and pneumonic plague. Bubonic plague is the main form and is characterized by enlarged purulent abscesses called ‘bubos’, which are caused by the massive reproduction of the Y. pestis After its rapid migration to dLNs after infection. Research related to paralysis of innate immune responses Y. pestis During the early stages of infection is limited, which has hampered our understanding of Y. pestis The way the disease develops.

Researchers challenge mice with fluorescent markers Y. pestis By subcutaneous injection into the groin of mice to simulate the development of bubonic plague. On this basis, they took mouse inguinal lymph nodes at 2second abbreviation hour 24The tenth Hour post-infection (hpi) and analysis of changes in the composition and status of immune cells in lymph nodes by flow cytometry and single cell transcript sequencing. Compared with the control group, the inflammation-related pathway genes were significantly upregulated in lymph node cells of infected mice. Y. pestis during the early stage of infection. The researchers calculated an infection preference index by the proportion of specific cells with fluorescent markers and found that Y. pestis They tend to interact with resident innate immune cells including dendritic cells, monocytes/macrophages and neutrophils, rather than adaptive immune cells.

Next, the researchers sorted out resident innate immune cells and performed our sugar sequencing. found that monocytes/macrophages showed activation of M1 and M2 coupling in response to Y. pestis Infection, which could be the overall results of the immune response activation mediated by host pattern recognition receptors and the inhibitory effects of different virulence factors. Y. pestis.

In addition, the team also used the CellPhoneDB-based Cell Interaction Analysis tool to detect ligand-receptor interaction of different cell types at different infection time points. It was found that the neutrophil chemokine receptor CCR1 may be involved in the recruitment of neutrophils to lymph nodes after infection, and CCR1 function inhibition experiments were performed to verify this conclusion.

Taken together, this study demonstrated the critical cell types involved and the critical immune events that occurred in the initial interactions between them Y. pestis and the host at the unicellular transcriptional level, which will be valuable for understanding the development of bubonic plague and the host’s immune response Y. pestis in the early stage.


Journal reference:

Chow, wai. et al. (2022) Single-cell transcripts of immune cells in lymph nodes reveal their formation and changes in functional dynamics during the early stages of bubonic plague. China Science Life Science.


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