Single-cell transcriptomics of immune cells in lymph nodes reveals their composition and alterations in functional dynamics during the early stages of bubonic plague.

Abstract

Bubonic plague caused by Yersinia pestis is highly infectious and often fatal. Characterization of the host immune response and its subsequent suppression by Y. pestis is critical to understanding the pathogenesis of Y. pestis. Here, we utilized single-cell RNA sequencing to systematically profile the transcriptomes of immune cells in draining lymph nodes (dLNs) during the early stage of Y. pestis infection. Dendritic cells responded to Y. pestis within 2 h post-infection (hpi), followed by the activation of macrophages/monocytes (Mφs/Mons) and recruitment of polymorphonuclear neutrophils (PMNs) to dLNs at 24 hpi. Analysis of cell-to-cell communication suggests that PMNs may be recruited to lymph nodes following the secretion of CCL9 by Mφs/Mons stimulated through CCR1-CCL9 interaction. Significant functional suppression of all the three innate immune cell types occurred during the early stage of infection. In summary, we present a dynamic immune landscape, at single-cell resolution, of murine dLNs involved in the response to Y. pestis infection, which may facilitate the understanding of the plague pathogenesis of during the early stage of infection.