{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:10:50Z","timestamp":1772521850182,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"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. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    pneumonia is marked by an excessive inflammatory response that drives lung injury. The initial stages of infection and the mechanisms driving hyper-inflammation at the airway epithelial barrier are not fully defined. The alarmins S100A8\/A9 are potent inflammatory mediators, and studies have indicated their importance in the host response to\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    . Here, we show that infection with live\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    directly induces the transcription and secretion of the S100A8\/A9 heterodimer in a primary human bronchial epithelial (HBE) cell model. Furthermore, the infection sensitizes epithelial cells by upregulating the expression of Toll-like receptor 4, a key receptor that mediates S100A8\/A9 signaling. We also established that HBE cells are highly responsive to extracellular S100A8\/A9, which stimulates pro-inflammatory cytokine production. Critically, silencing of endogenous S100A9 expression in HBE cells significantly attenuated NF-\u03baB activation and the overall cytokine response to bacterial infection, providing direct evidence for an epithelium-intrinsic autocrine amplification loop. Functionally, disruption of this loop markedly reduced the ability of epithelial cell supernatants to induce neutrophil chemotaxis. These findings reveal a novel autocrine mechanism that positions the airway epithelium not just as a responder, but as an active initiator and amplifier of local inflammation during early\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1768140","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:49:45Z","timestamp":1772520585000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Klebsiella pneumoniae infection induces an S100A8\/A9-mediated autocrine loop in human airway epithelium to amplify inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jie","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical College, University of South China","place":["Hengyang, China"]},{"name":"Department of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical College, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuchan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical College, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianrui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, Hengyang Medical College, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shutong","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institute of Pathogenic Biology, Hengyang Medical College, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caihong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical College, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical College, University of South China","place":["Hengyang, China"]},{"name":"Department of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical College, University of South China","place":["Hengyang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e1002987","DOI":"10.1371\/journal.ppat.1002987","article-title":"Myeloid-related protein-14 contributes to protective immunity in gram-negative pneumonia derived sepsis","volume":"8","author":"Achouiti","year":"2012","journal-title":"PLoS Pathog."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"112184","DOI":"10.1016\/j.biopha.2021.112184","article-title":"IL-17 stimulates neutrophils to release S100A8\/A9 to promote lung epithelial cell apoptosis in Mycoplasma pneumoniae-induced pneumonia in children","volume":"143","author":"Bai","year":"2021","journal-title":"Biomed. 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Lung Res."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e1011233","DOI":"10.1371\/journal.ppat.1011233","article-title":"Klebsiella pneumoniae causes bacteremia using factors that mediate tissue-specific fitness and resistance to oxidative stress","volume":"19","author":"Holmes","year":"2023","journal-title":"PLoS Pathog."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1186\/s12879-023-08528-x","article-title":"Prognostic models for estimating severity of disease and predicting 30-day mortality of hypervirulent Klebsiella pneumoniae infections: a bicentric retrospective study","volume":"23","author":"Huang","year":"2023","journal-title":"BMC Infect. 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Drug Resist."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/cei.13510","article-title":"Mycoplasma pneumoniae lipids license TLR-4 for activation of NLRP3 inflammasome and autophagy to evoke a proinflammatory response","volume":"203","author":"Luo","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"31","DOI":"10.3892\/ijmm.2017.2987","article-title":"Proinflammatory effects of S100A8\/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells","volume":"40","author":"Ma","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1183\/09031936.06.00010806","article-title":"Toll-like receptor mRNA levels in alveolar macrophages after inhalation of endotoxin","volume":"28","author":"Maris","year":"2006","journal-title":"Eur. Respir. 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Infect."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"6975","DOI":"10.2147\/IDR.S378753","article-title":"Lumbar cistern drainage and gentamicin intrathecal injection in the treatment of carbapenem-resistant Klebsiella pneumoniae intracranial infection after intracerebral hemorrhage craniotomy: a case report","volume":"15","author":"Zhou","year":"2022","journal-title":"Infect. Drug Resist."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1768140\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:49:46Z","timestamp":1772520586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1768140\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":36,"alternative-id":["10.3389\/fmicb.2026.1768140"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1768140","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]},"article-number":"1768140"}}