{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:26:41Z","timestamp":1791188801076,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Respiratory virus infections cause airway hyperreactivity (AHR). Preventative strategies for virus-induced AHR remain limited. Toll-like receptors (TLRs) have been suggested as a therapeutic target because of their central role in triggering antiviral immune responses. Previous studies showed that concurrent treatment with TLR2\/6 and TLR9 agonists reduced lethality and the microbial burden in murine models of bacterial and viral pneumonia. This study investigated the effects of TLR2\/6 and TLR9 agonist pretreatment on parainfluenza virus pneumonia and virus-induced AHR in guinea pigs in vivo. Synthetic TLR2\/6 lipopeptide agonist Pam2CSK4 and Class C oligodeoxynucleotide TLR9 agonist ODN2395, administered in combination 24 hours before virus infection, significantly reduced viral replication in the lung. Despite a fivefold reduction in viral titers, concurrent TLR2\/6 and TLR9 agonist pretreatment did not prevent virus-induced AHR or virus-induced inhibitory M2 muscarinic receptor dysfunction. Interestingly, the TLR agonists independently caused non\u2013M2-dependent AHR. These data confirm the therapeutic antiviral potential of TLR agonists, while suggesting that virus inhibition may be insufficient to prevent virus-induced airway pathophysiology. Furthermore, TLR agonists independently cause AHR, albeit through a distinctly different mechanism from that of parainfluenza virus.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0498oc","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T12:26:03Z","timestamp":1362140763000},"page":"790-796","source":"Crossref","is-referenced-by-count":19,"title":["Toll-Like Receptor\u20132\/6 and Toll-Like Receptor\u20139 Agonists Suppress Viral Replication but Not Airway Hyperreactivity in Guinea Pigs"],"prefix":"10.1093","volume":"48","author":[{"given":"Matthew G.","family":"Drake","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton F.","family":"Dickey","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison D.","family":"Fryer","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, and"},{"name":"Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, 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