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Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522048/
https://www.ncbi.nlm.nih.gov/pubmed/37695784
http://dx.doi.org/10.1371/journal.ppat.1011138
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author 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.
author_facet 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.
author_sort Wang, Yongxing
collection PubMed
description 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.
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spelling pubmed-105220482023-09-27 Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation 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. PLoS Pathog Research Article 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. Public Library of Science 2023-09-11 /pmc/articles/PMC10522048/ /pubmed/37695784 http://dx.doi.org/10.1371/journal.ppat.1011138 Text en © 2023 Wang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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.
Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
title Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
title_full Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
title_fullStr Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
title_full_unstemmed Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
title_short Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
title_sort antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522048/
https://www.ncbi.nlm.nih.gov/pubmed/37695784
http://dx.doi.org/10.1371/journal.ppat.1011138
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