{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:35:28Z","timestamp":1786534528878,"version":"build-2736575974"},"reference-count":188,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes (cGAS\u2013STING) signaling pathway plays a pivotal role in mediating both infectious and sterile pulmonary inflammation, exhibiting distinct dynamic characteristics under different contexts. The activation kinetics of the cGAS\u2013STING pathway are highly dependent on disease context. In many acute infections, the cGAS\u2013STING pathway is often activated rapidly and induces a strong type I interferon (IFN-I) response, which helps control pathogens. In contrast, chronic sterile injury is usually associated with endogenous damage-associated molecular patterns (DAMPs), persistent low-level pathway activation, inflammatory remodeling, and fibrosis. However, these patterns should be viewed as two ends of a dynamic infectious\u2013sterile continuum rather than as mutually exclusive categories. In many pulmonary diseases, including tuberculosis, chronic viral infection, chronic obstructive pulmonary disease (COPD) exacerbation, infection-associated acute respiratory distress syndrome (ARDS), and post-infectious fibrosis, infectious and sterile mechanisms may coexist, overlap, or occur sequentially. This review summarizes the similarities, differences, and mechanistic connections between cGAS\u2013STING signaling in infectious and sterile lung inflammation. We focus on upstream triggers, signaling dynamics, cell-specific responses, intercellular cyclic GMP-AMP (cGAMP) transmission, inflammatory outcomes, biomarkers, and therapeutic implications. We also propose a temporal\u2013intensity model of cGAS\u2013STING signaling as a conceptual framework to better understand stage-specific pathway functions and support future translational research.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1867680","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T10:59:36Z","timestamp":1786532376000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The cGAS\u2013STING pathway in pulmonary infectious and sterile inflammation: differences, connections, and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Chenglin","family":"Liu","sequence":"first","affiliation":[{"name":"The Second Clinical Medical College, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lannan","family":"Yang","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical 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