Details

Autor(en) / Beteiligte

• Wang, Yongxing
• Kulkarni, Vikram V
• Pantaleón García, Jezreel
• Leiva-Juárez, Miguel M
• Goldblatt, David L
• Gulraiz, Fahad
• Vila Ellis, Lisandra
• Chen, Jichao
• Longmire, Michael K
• Donepudi, Sri Ramya
• Lorenzi, Philip L
• Wang, Hao
• Wong, Lee-Jun
• Tuvim, Michael J
• Evans, Scott E
• Guillard, Thomas

Titel

Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation

Ist Teil von

• PLoS pathogens, 2023-09, Vol.19 (9), p.e1011138-e1011138

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2023

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs’ intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (Δ Ψm ), differentially modulates ETC complex activities and consequently results in leak of electrons from ETC complex III and superoxide formation. The ODN-induced mitochondrial ROS yield protective antibacterial effects. Together, these studies identify a therapeutic metabolic manipulation strategy to broadly protect against pneumonia without reliance on antibiotics.