The dynamic immune cell landscape in the lungs of Pneumocystis infected mice

Pneumocystis pneumonia is an opportunistic pneumonia that has been increasing in non-HIV patients in recent years. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis, we profile the transcriptomes of mouse lungs with Pneumocystis pneumonia and from uninfected control subjects using single-cell RNA sequencing, yielding multiple populations of myeloid cells, T cells and B cells. We uncover a PCP-associated TREM2+ subpopulation of interstitial macrophages, which expands in PCP, differentiates from Ly6C+ monocytes. We also define the subsets of effector CD4+ T cells that expand after the infection of Pneumocystis. Finally, intercellular crosstalk between interstitial macrophages and effector CD4+ T cells via multiple ligand and receptor interactions reveals several anti-pneumocystis pathways. Our work dissects unanticipated aspects of the cellular and molecular basis of Pneumocystis pneumonia at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in Pneumocystis pneumonia. Single-cell RNA profiles of wild type (WT) and mices infected with Pneumocystis 1-4 weeks.