{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:33:13Z","timestamp":1784248393304,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"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>Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils <jats:italic>in vitro<\/jats:italic>. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to <jats:italic>Klebsiella pneumoniae.<\/jats:italic> In addition, priming of human lung tissue <jats:italic>ex vivo<\/jats:italic> with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of <jats:italic>Klebsiella pneumoniae<\/jats:italic> in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.<\/jats:p>","DOI":"10.3389\/fimmu.2021.761317","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T09:25:10Z","timestamp":1635413110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Complex Involvement of Interleukin-26 in Bacterial Lung Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Karlhans F.","family":"Che","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Paulsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Piersiala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Sax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Mboob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizanur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rokeya S.","family":"Rekha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"S\u00e4fholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Adner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-Olaf","family":"Cardell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Riesbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Lind\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/nrmicro2273","article-title":"Closing the GAPP on Pneumonia","volume":"7","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.prrv.2015.08.004","article-title":"Vaccines to Prevent Pneumonia in Children - a Developing Country Perspective","volume":"22","author":"Oliwa","year":"2017","journal-title":"Paediatr Respir Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.07.005","article-title":"Host Defenses Against Bacterial Lower Respiratory Tract Infection","volume":"24","author":"Eddens","year":"2012","journal-title":"Curr Opin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.05.00009504","article-title":"Impact of Bacterial Infections on Airway Diseases","volume":"14","author":"Toews","year":"2005","journal-title":"Eur Respir Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.3.1093","article-title":"Staphylococcus Aureus Pneumonia: A \"Superbug\" Infection in Community and Hospital Settings","volume":"128","author":"Kollef","year":"2005","journal-title":"Chest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cytogfr.2020.10.003","article-title":"Interleukin-26 in Host Defense and Inflammatory Disorders of the Airways","volume":"57","author":"Che","year":"2020","journal-title":"Cytokine Growth Factor Rev"},{"key":"B7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1159\/000434646","article-title":"Interleukin-26: An Emerging Player in Host Defense and Inflammation","volume":"8","author":"Tengvall","year":"2016","journal-title":"J Innate Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1042\/CS20180057","article-title":"The Neutrophil-Mobilizing Cytokine Interleukin-26 in the Airways of Long-Term Tobacco Smokers","volume":"132","author":"Che","year":"2018","journal-title":"Clin Sci (Lond)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201404-0689OC","article-title":"Interleukin-26 in Antibacterial Host Defense of Human Lungs. 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