Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections

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dc.citation.articleNumbere0208216en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitlePLOS ONEen_US
dc.citation.volumeNumber14en_US
dc.contributor.authorWare, Hayden H.en_US
dc.contributor.authorKulkarni, Vikram V.en_US
dc.contributor.authorWang, Yongxingen_US
dc.contributor.authorGarcía, Jezreel Pantaleónen_US
dc.contributor.authorJuarez, Miguel Leivaen_US
dc.contributor.authorKirkpatrick, Carson T.en_US
dc.contributor.authorWali, Shradhaen_US
dc.contributor.authorSyed, Sarahen_US
dc.contributor.authorKontoyiannis, Alexander D.en_US
dc.contributor.authorSikkema, William K. A.en_US
dc.contributor.authorTour, James M.en_US
dc.contributor.authorEvans, Scott E.en_US
dc.contributor.orgSmalley Institute for Nanoscale Science and Technologyen_US
dc.date.accessioned2021-10-19T15:35:29Zen_US
dc.date.available2021-10-19T15:35:29Zen_US
dc.date.issued2019en_US
dc.description.abstractPneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation of the lungs’ mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against a bacterial pathogen and provide mechanistic insights into means to protect vulnerable patients against lethal infections.en_US
dc.identifier.citationWare, Hayden H., Kulkarni, Vikram V., Wang, Yongxing, et al.. "Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections." <i>PLOS ONE,</i> 14, no. 2 (2019) Public Library of Science: https://doi.org/10.1371/journal.pone.0208216.en_US
dc.identifier.digitalpone-0208216en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0208216en_US
dc.identifier.urihttps://hdl.handle.net/1911/111574en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleInducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infectionsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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