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

PloS One
Hayden H WareScott E Evans

Abstract

Pneumonia 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 genera...Continue Reading

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Citations

Jul 22, 2020·BMC Microbiology·Ker-Kong ChenKazunari K Yokoyama
Mar 3, 2020·Frontiers in Immunology·Lokesh SharmaCharles S Dela Cruz
Aug 28, 2020·American Journal of Respiratory Cell and Molecular Biology·Shradha WaliScott E Evans
Jun 22, 2021·Frontiers in Immunology·Alexia Dumas, Ulla G Knaus
Nov 4, 2021·Biomedit︠s︡inskai︠a︡ khimii︠a︡·V V SalminA B Salmina

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Methods Mentioned

BETA
bronchoalveolar lavage
transfection

Software Mentioned

SPSS

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