{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:23:44Z","timestamp":1793046224441,"version":"4.5.0"},"reference-count":148,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"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:p>Severe pneumonia-associated lung injury remains a critical focus in infection and immunology research due to its high lethality and complex immunopathology. Affected patients often present with cellular immune deficiency and an imbalanced interplay between pro-inflammatory and anti-inflammatory mediators, with infection-immunity disequilibrium driving disease progression. The initial infection triggers a defense-injury cascade: while inflammation facilitates pathogen clearance, persistent or excessive activation leads to progressive lung tissue damage. Recent advances have deepened our understanding of immune mechanisms and inflammatory regulation; however, key challenges persist in clinical translation. Here, we synthesize current evidence on the immunopathology of severe pneumonia-associated lung injury, dissect the hierarchical architecture of its molecular regulatory networks, and critically appraise existing therapeutic strategies and their limitations. We propose a translational framework\u2014encompassing mechanistic research, network modelling, and precision intervention\u2014to guide stage-specific regulation and targeted therapy. Finally, we outline the major challenges impeding the clinical application of basic immunological discoveries and highlight future directions for improving patient outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1702084","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:26:30Z","timestamp":1773725190000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Advances in infection-immunity mechanisms and molecular regulatory networks in severe pneumonia-associated lung injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Second Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gao","sequence":"additional","affiliation":[{"name":"Second Department of 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