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Classical monocytes emerged as central orchestrators of the cytokine storm observed in severe cases, displaying elevated expression of proinflammatory genes (e.g., S100A8\/9\/12) and enhanced TLR4-MYD88 signaling. Exhaustion of innate-like CD8+ T cells, marked by upregulation of canonical inhibitory receptors, was a hallmark of severe disease. In contrast, mild pneumonia exhibited robust CD8+ T effector and helper memory cell activation, together with effective humoral immunity, evidenced by plasma cell expansion and coordinated T follicular helper cell\u2013B cell interactions. B cells in mild cases showed enhanced antigen recognition, BCR signaling, and costimulatory gene expression, whereas those in severe cases displayed signs of dysfunction. Myeloid cell alterations in severe pneumonia included increased monocytic myeloid-derived suppressor cells and nonclassical monocytes, contributing to immunosuppression and complement overactivation, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This high-resolution atlas of peripheral immune responses in bacterial pneumonia identifies key cellular and molecular drivers of disease severity, providing potential therapeutic targets for immunomodulation and improved outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202501-0217oc","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T17:18:12Z","timestamp":1754327892000},"page":"2363-2381","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":29,"title":["A Large-Scale Single-Cell Atlas Reveals the 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