{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:34:09Z","timestamp":1782448449812,"version":"3.54.5"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HL117976,DP2 HL123229,R35 HL144805"],"award-info":[{"award-number":["R01 HL117976,DP2 HL123229,R35 HL144805"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,8]]},"abstract":"<jats:p>Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in TLR9, the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, and we discovered by mass spectroscopy that the RNA sensor RIG-I could also bind DNA-like ODN. ODN binding by RIG-I resulted in MAVS-dependent pneumonia-protective signaling events. While RIG-I is essential to native defenses against viral infections, we report that therapeutic RIG-I activation with ODN promoted pathogen killing and host survival following both viral and bacterial challenges. These data indicate that maximal ODN-induced pneumonia protection requires activation of both the TLR9\/MyD88 and RIG-I\/MAVS signaling pathways. These findings not only identify what we believe to be a novel pattern recognition receptor for DNA-like molecules, but reveal a potential therapeutic strategy to protect susceptible individuals against lethal pneumonias during periods of peak vulnerability.<\/jats:p>","DOI":"10.1172\/jci.insight.180584","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T12:00:29Z","timestamp":1727784029000},"source":"Crossref","is-referenced-by-count":5,"title":["The RNA receptor RIG-I binding synthetic oligodeoxynucleotide promotes pneumonia survival"],"prefix":"10.1172","volume":"9","author":[{"given":"Yongxing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram V.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, UTHealth Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jezreel","family":"Pantale\u00f3nGarc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Longmire","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, UTHealth Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Lethier","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Cusack","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Grenoble, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-0644","authenticated-orcid":true,"given":"Scott E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, UTHealth Houston, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00259-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202212-1019ST"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00687-0"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.71"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.749077"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0247LE"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14977"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208216"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00696-18"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-708511"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.26"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002122"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0260OC"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030596"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqac028"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100301.064842"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12039"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-005-6605-0"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0244-x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011138"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0288-3"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00602-7"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.015"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1779"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3673-1_7"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.04.010"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2022-0342OC"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2016.03.007"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.10.035"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107114108"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180508"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2019.11.001"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.9b00895"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200607-1038OC"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004176"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/med.21845"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.11.008"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/180584\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:38:24Z","timestamp":1779136704000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/180584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":39,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11,8]]},"published-print":{"date-parts":[[2024,11,8]]}},"alternative-id":["10.1172\/jci.insight.180584"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.180584","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]},"article-number":"e180584"}}