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

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dc.citation.articleNumbere0208216
dc.citation.issueNumber2
dc.citation.journalTitlePLOS ONE
dc.citation.volumeNumber14
dc.contributor.authorWare, Hayden H.
dc.contributor.authorKulkarni, Vikram V.
dc.contributor.authorWang, Yongxing
dc.contributor.authorGarcía, Jezreel Pantaleón
dc.contributor.authorJuarez, Miguel Leiva
dc.contributor.authorKirkpatrick, Carson T.
dc.contributor.authorWali, Shradha
dc.contributor.authorSyed, Sarah
dc.contributor.authorKontoyiannis, Alexander D.
dc.contributor.authorSikkema, William K. A.
dc.contributor.authorTour, James M.
dc.contributor.authorEvans, Scott E.
dc.contributor.orgSmalley Institute for Nanoscale Science and Technology
dc.date.accessioned2021-10-19T15:35:29Z
dc.date.available2021-10-19T15:35:29Z
dc.date.issued2019
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.
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.
dc.identifier.digitalpone-0208216
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0208216
dc.identifier.urihttps://hdl.handle.net/1911/111574
dc.language.isoeng
dc.publisherPublic Library of Science
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleInducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against bacterial infections
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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