Single-cell multiomics reveals a CD4+ TH1 driven response to Pneumocystis in immunocompetent hosts

We used a co-housing exposure model of mouse Pneumocystis (P. murina) infection to characterize the roles of pulmonary immune cell populations in immunocompetent (C57BL/6) mice at single-cell level. CD4+ TH1 cells showed the greatest increase and clonal expansion following P. murina infection, with less pronounced increases in TH17 and TfH cells.

We also observed reduced TCR diversity post-P. murina infection, and identified expanded clonotypes with limited overlap between animals, suggesting antigenic variation. Infected mice showed differential expression of pro-inflammatory cytokines IL-21, Cxcl9, Ly6a, co-stimulatory molecule Ox-40 (CD134), and regulatory genes Lag3 and Ctla4, indicating a regulated immune response. Pathway analyses predicted IFN‐γ centered cytokine interactions which presumably enhance killing of P. murina organisms by macrophages.