Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/120695
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dc.contributor.author | To, E.E. | - |
dc.contributor.author | Erlich, J.R. | - |
dc.contributor.author | Liong, F. | - |
dc.contributor.author | Luong, R. | - |
dc.contributor.author | Liong, S. | - |
dc.contributor.author | Esaq, F. | - |
dc.contributor.author | Oseghale, O. | - |
dc.contributor.author | Anthony, D. | - |
dc.contributor.author | McQualter, J. | - |
dc.contributor.author | Bozinovski, S. | - |
dc.contributor.author | Vlahos, R. | - |
dc.contributor.author | O'Leary, J.J. | - |
dc.contributor.author | Brooks, D.A. | - |
dc.contributor.author | Selemidis, S. | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Antioxidants and Redox Signaling, 2019; 32(13) | - |
dc.identifier.issn | 1523-0864 | - |
dc.identifier.issn | 1557-7716 | - |
dc.identifier.uri | http://hdl.handle.net/2440/120695 | - |
dc.description.abstract | Aims: Reactive oxygen species (ROS) are highly reactive molecules generated in different subcellular sites or compartments, including endosomes via the NOX2-containing nicotinamide adenine dinucleotide phosphate oxidase during an immune response and in mitochondria during cellular respiration. However, while endosomal NOX2 oxidase promotes innate inflammation to influenza A virus (IAV) infection, the role of mitochondrial ROS (mtROS) has not been comprehensively investigated in the context of viral infections in vivo. Results: In this study, we show that pharmacological inhibition of mtROS, with intranasal delivery of MitoTEMPO, resulted in a reduction in airway/lung inflammation, neutrophil infiltration, viral titers, as well as overall morbidity and mortality in mice infected with IAV (Hkx31, H3N2). MitoTEMPO treatment also attenuated apoptotic and necrotic neutrophils and macrophages in airway and lung tissue. At an early phase of influenza infection, that is, day 3 there were significantly lower amounts of IL-1β protein in the airways, but substantially higher amounts of type I IFN-β following MitoTEMPO treatment. Importantly, blocking mtROS did not appear to alter the initiation of an adaptive immune response by lung dendritic cells, nor did it affect lung B and T cell populations that participate in humoral and cellular immunity. Innovation/Conclusion: Influenza virus infection promotes mtROS production, which drives innate immune inflammation and this exacerbates viral pathogenesis. This pathogenic cascade highlights the therapeutic potential of local mtROS antioxidant delivery to alleviate influenza virus pathology. | - |
dc.description.statementofresponsibility | Eunice E. To, Jonathan R. Erlich, Felicia Liong, Raymond Luong, Stella Liong, Farisha Esaq, Osezua Oseghale, Desiree Anthony, Jonathan McQualter, Steven Bozinovski, Ross Vlahos, John J. O, Leary, Doug A. Brooks, and Stavros Selemidis | - |
dc.language.iso | en | - |
dc.publisher | Mary Ann Liebert | - |
dc.rights | © Eunice E. To et al., 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | - |
dc.source.uri | http://dx.doi.org/10.1089/ars.2019.7727 | - |
dc.subject | influenza | - |
dc.subject | lung inflammation | - |
dc.subject | mitochondria | - |
dc.subject | reactive oxygen species | - |
dc.title | Mitochondrial reactive oxygen species contribute to pathological inflammation during influenza a virus infection in mice | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1089/ars.2019.7727 | - |
dc.relation.grant | http://purl.org/au-research/grants/arc/FT120100876 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1122506 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1128276 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Brooks, D.A. [0000-0001-9098-3626] | - |
Appears in Collections: | Aurora harvest 4 Biochemistry publications |
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hdl_120695.pdf | Published version | 697.79 kB | Adobe PDF | View/Open |
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