This study is led by Dr. Ruifu Yang, Dr. Zongmin Du (State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology) and Dr. Fan Bai (Biomedical Pioneering Innovation Center, School of Life Sciences, Peking University).

Yersinia pestis (Y. pestis), the causative agent of plague, has caused hundreds of thousands of deaths in three worldwide pandemics in history. Plague is predominately a flea-borne zoonotic disease. While only sporadic human plague outbreaks occur around the globe annually, the specter of plague to humans and society mustn’t be underestimated. Three subtypes of the disease are commonly encountered within the clinic, namely bubonic, septicemic, and pneumonic plagues. Bubonic plague is the main form and is characterised by enlarged purulent abscesses called “buboes”, that are attributable to the large replication of Y. pestis after its rapid migration into the dLNs post infection. Relevant research on paralysis of the innate immune responses by Y. pestis throughout the early stages of infection is proscribed, which has hindered our understanding of Y. pestis pathogenesis.

The researchers challenged mice with fluorescent-labeled Y. pestis by subcutaneous injection into the groins of mice to simulate the bubonic plague development. On this basis, they took mouse inguinal lymph nodes on the 2nd hour and the twenty fourth hour post infection (hpi) and analyzed the changes within the composition and standing of immune cells within the lymph nodes by flow cytometry and single-cell transcriptome sequencing. Compared with the control group, genes of the inflammation related pathway were significantly up-regulated within the lymph node cells of mice infected with Y. pestis throughout the early stage of infection. The researchers calculated the infection preference index by the proportion of specific fluorescent labeled cells and located that Y. pestis are inclined to interact with the resident innate immune cells including dendritic cells, monocytes/macrophages and neutrophils, moderately than adaptive immune cells.

Subsequently, the researchers further sorted the resident innate immune cells and performed the scRNA-seq. It was found that monocytes/macrophages showed M1 and M2 coupling activation in response to Y. pestis infection, which may very well be the great results of the activation of immune response mediated by host pattern recognition receptors and the inhibition effects of assorted virulence aspects of Y. pestis.

As well as, the team also used the cell interaction evaluation tool based on CellPhoneDB to disclose the ligand receptor interaction of various cell types at different infection time points. It was found that the chemokine receptor CCR1 of neutrophils could also be involved within the recruitment of neutrophils to lymph nodes post infection, and the CCR1 function inhibition experiments were performed to confirm this conclusion.

Taken together, this study demonstrated the critical cell types involved and significant immune events occurred within the initial interactions between Y. pestis and the host on the single-cell transcription level, which might be invaluable for understanding the event of bubonic plague and host immune response to Y. pestis on the early stage.

Source:

Journal reference:

Zhao, Y., et al. (2022) Single-cell transcriptomics of immune cells in lymph nodes reveals their composition and alterations in functional dynamics throughout the early stages of bubonic plague. Science China Life Sciences. doi.org/10.1007/s11427-021-2119-5.