Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia.
Identifieur interne : 000B65 ( Main/Exploration ); précédent : 000B64; suivant : 000B66Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia.
Auteurs : Keer Sun [États-Unis] ; Vijaya Kumar Yajjala [États-Unis] ; Christopher Bauer [États-Unis] ; Geoffrey A. Talmon [États-Unis] ; Karl J. Fischer [États-Unis] ; Tammy Kielian [États-Unis] ; Dennis W. Metzger [États-Unis]Source :
- The Journal of experimental medicine [ 1540-9538 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Antibactériens (usage thérapeutique), Cellules myéloïdes (physiologie), Espèces réactives de l'oxygène (métabolisme), Femelle, Glycoprotéines membranaires (physiologie), Infections à Orthomyxoviridae (), Inflammation (étiologie), Mâle, Pneumopathie à staphylocoques (traitement médicamenteux), Souris, Souris de lignée C57BL, Staphylococcus aureus résistant à la méticilline, Stress oxydatif, Survie cellulaire.
- MESH :
- métabolisme : Espèces réactives de l'oxygène.
- physiologie : Cellules myéloïdes, Glycoprotéines membranaires.
- traitement médicamenteux : Pneumopathie à staphylocoques.
- usage thérapeutique : Antibactériens.
- étiologie : Inflammation.
- Animaux, Femelle, Infections à Orthomyxoviridae, Mâle, Souris, Souris de lignée C57BL, Staphylococcus aureus résistant à la méticilline, Stress oxydatif, Survie cellulaire.
English descriptors
- KwdEn :
- Animals, Anti-Bacterial Agents (therapeutic use), Cell Survival, Female, Inflammation (etiology), Male, Membrane Glycoproteins (physiology), Methicillin-Resistant Staphylococcus aureus, Mice, Mice, Inbred C57BL, Myeloid Cells (physiology), NADPH Oxidase 2, NADPH Oxidases (physiology), Orthomyxoviridae Infections (complications), Oxidative Stress, Pneumonia, Staphylococcal (drug therapy), Reactive Oxygen Species (metabolism).
- MESH :
- chemical , metabolism : Reactive Oxygen Species.
- chemical , physiology : Membrane Glycoproteins, NADPH Oxidases.
- chemical , therapeutic use : Anti-Bacterial Agents.
- complications : Orthomyxoviridae Infections.
- drug therapy : Pneumonia, Staphylococcal.
- etiology : Inflammation.
- physiology : Myeloid Cells.
- Animals, Cell Survival, Female, Male, Methicillin-Resistant Staphylococcus aureus, Mice, Mice, Inbred C57BL, NADPH Oxidase 2, Oxidative Stress.
Abstract
Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.
DOI: 10.1084/jem.20150514
PubMed: 27526712
Affiliations:
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In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Nebraska</li><li>État de New York</li></region></list><tree><country name="États-Unis"><noRegion><name sortKey="Sun, Keer" sort="Sun, Keer" uniqKey="Sun K" first="Keer" last="Sun">Keer Sun</name></noRegion><name sortKey="Bauer, Christopher" sort="Bauer, Christopher" uniqKey="Bauer C" first="Christopher" last="Bauer">Christopher Bauer</name><name sortKey="Fischer, Karl J" sort="Fischer, Karl J" uniqKey="Fischer K" first="Karl J" last="Fischer">Karl J. Fischer</name><name sortKey="Kielian, Tammy" sort="Kielian, Tammy" uniqKey="Kielian T" first="Tammy" last="Kielian">Tammy Kielian</name><name sortKey="Metzger, Dennis W" sort="Metzger, Dennis W" uniqKey="Metzger D" first="Dennis W" last="Metzger">Dennis W. Metzger</name><name sortKey="Talmon, Geoffrey A" sort="Talmon, Geoffrey A" uniqKey="Talmon G" first="Geoffrey A" last="Talmon">Geoffrey A. Talmon</name><name sortKey="Yajjala, Vijaya Kumar" sort="Yajjala, Vijaya Kumar" uniqKey="Yajjala V" first="Vijaya Kumar" last="Yajjala">Vijaya Kumar Yajjala</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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