{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:27Z","timestamp":1788844227379,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      pneumonia triggers a complex, dynamic host response, yet the cellular coordination of inflammation and repair remains poorly defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed time-resolved single-cell RNA sequencing (scRNA-seq) on murine lungs across five timepoints (0\u201396 h post-infection) and integrated these data with spatial transcriptomics (10x Visium) performed on matched tissue sections at key timepoints (0, 24, and 96 h), profiling a total of 41,452 high-quality cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified four neutrophil subsets, with the N3 population exhibiting potent antimicrobial activity. We traced the emergence of inflammatory fibroblasts during acute infection to Col13a1\n                      <jats:sup>+<\/jats:sup>\n                      matrix fibroblasts, a process driven by a regulatory network centered on Stat1 and Nfkb1. Spatial transcriptomics with RCTD deconvolution revealed a 22.5% peak immune infiltration at 24 h, while COMMOT analysis uncovered 30-fold and 25-fold increases in\n                      <jats:italic>Ccl2\u2013Ccr2 and Cxcl2\u2013Cxcr2<\/jats:italic>\n                      spatial signaling, respectively, pinpointing chemokine-driven recruitment foci. Notably, spatial mapping distinguished tissue remodeling activity from cell-type abundance, identifying acute matrix remodeling zones dominated by\n                      <jats:italic>Timp1<\/jats:italic>\n                      rather than canonical fibroblast markers. Alveolar type 2 epithelial cells transitioned through three distinct states\u2014homeostatic, inflammatory, and reparative. Notably, the circadian gene\n                      <jats:italic>Dbp<\/jats:italic>\n                      was specifically upregulated at 96 h, suggesting a role for circadian programs in resolution of pathology. Crucially, we uncovered a pivotal role for group 2 innate lymphoid cells (ILC2s): epithelial-derived IL-33 activated ILC2s via the ST2 receptor (\n                      <jats:italic>Il1rl1<\/jats:italic>\n                      ) during acute infection (24 hpi), promoting a type 2 immune response that limits immunopathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our integrative time-resolved spatial transcriptomic atlas elucidates how structural and immune cells orchestrate the balance between bacterial clearance and tissue repair, highlighting novel targets for host-directed therapies in\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      pneumonia.\n                    <\/jats:p>\n                  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