Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial Toxin-Mediated Necroptosis

Riegler, Ashleigh N.; Jureka, Alexander S.; Gilley, Ryan P.; Brand, Jeffrey D.; Trombley, John E.; Scott, Ninecia R.; Dube, Peter H.; Petit, Chad M.; Harrod, Kevin S.; Orihuela, Carlos J.

doi:10.2139/ssrn.3565039

Cited by 4 publications

(12 citation statements)

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“…Virus-induced oxidative stress via the generation of reactive oxygen species (ROS) is also a factor that increases the expression of proinflammatory cytokines and chemokines [ 31 ] and sensitizes lung cells to bacteria toxin-mediated necroptosis [ 32 ]. The heightened neutrophil influx and cytokine storm coupled with subsequent ARDS correlates with multi-organ damage and mortality among COVID-19 patients [ 28 ].…”

Section: Immunopathogenesis Of Vrismentioning

confidence: 99%

“…The antiviral effects of polyphenols have been demonstrated to be mediated either by direct inhibitory effects on virus replication or through the induction of immunomodulatory/antioxidant responses [ 170 , 171 ]. Oxidative stress has been implicated in lung tissue injury and epithelial barrier dysfunction in acute respiratory viral infections [ 31 , 32 ]. Accumulating evidence has revealed the excellent immunomodulatory effects of epigallocatechin-3-gallate (EGCG), abundant in green tea on both innate and adaptive immune responses [ 173 ].…”

Section: Polyphenolic Plant Bioactivesmentioning

confidence: 99%

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Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

et al. 2020

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Viral respiratory infections (VRIs) can spread quickly and cause enormous morbidity and mortality worldwide. These events pose serious threats to public health due to time lags in developing vaccines to activate the acquired immune system. The high variability of people’s symptomatic responses to viral infections, as illustrated in the current COVID-19 pandemic, indicates the potential to moderate the severity of morbidity from VRIs. Growing evidence supports roles for probiotic bacteria (PB) and prebiotic dietary fiber (DF) and other plant nutritional bioactives in modulating immune functions. While human studies help to understand the epidemiology and immunopathology of VRIs, the chaotic nature of viral transmissions makes it difficult to undertake mechanistic study where the pre-conditioning of the metabolic and immune system could be beneficial. However, recent experimental studies have significantly enhanced our understanding of how PB and DF, along with plant bioactives, can significantly modulate innate and acquired immunity responses to VRIs. Synbiotic combinations of PB and DF potentiate increased benefits primarily through augmenting the production of short-chain fatty acids (SCFAs) such as butyrate. These and specific plant polyphenolics help to regulate immune responses to both restrain VRIs and temper the neutrophil response that can lead to acute respiratory distress syndrome (ARDS). This review highlights the current understanding of the potential impact of targeted nutritional strategies in setting a balanced immune tone for viral clearance and reinforcing homeostasis. This knowledge may guide the development of public health tactics and the application of functional foods with PB and DF components as a nutritional approach to support countering VRI morbidity.

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Section: Immunopathogenesis Of Vrismentioning

confidence: 99%

Section: Polyphenolic Plant Bioactivesmentioning

confidence: 99%

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

et al. 2020

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“…49 Influenza A has been shown to sensitize lung epithelial cells to bacteria poreforming toxin-mediated necroptosis, resulting in lung tissue damage. 53 Factors that increase post-influenza susceptibility to bacterial infection are summarized in ►Fig. 2.…”

Section: Co-infection Bacterialmentioning

confidence: 99%

Management of Severe Influenza

O'Driscoll¹,

Martín‐Loeches

2021

Semin Respir Crit Care Med

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Influenza infection causes severe illness in 3 to 5 million people annually, with up to an estimated 650,000 deaths per annum. As such, it represents an ongoing burden to health care systems and human health. Severe acute respiratory infection can occur, resulting in respiratory failure requiring intensive care support. Herein we discuss diagnostic approaches, including development of CLIA-waived point of care tests that allow rapid diagnosis and treatment of influenza. Bacterial and fungal coinfections in severe influenza pneumonia are associated with worse outcomes, and we summarize the approach and treatment options for diagnosis and treatment of bacterial and Aspergillus coinfection. We discuss the available drug options for the treatment of severe influenza, and treatments which are no longer supported by the evidence base. Finally, we describe the supportive management and ventilatory approach to patients with respiratory failure as a result of severe influenza in the intensive care unit.

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Section: Introduction (826 Words)mentioning

confidence: 99%

“…Mechanistic studies indicate that increased bacterial colonization is a consequence of upregulation of bacterial receptors and IAV-induced increases in sialic acid, which serves as a nutrient source for Spn (McCullers & Rehg, 2002; Mina & Klugman, 2014; Siegel, Roche, & Weiser, 2014). Further, enhanced bacterial systemic dissemination is facilitated by virus induced cytokine release, oxidative stress and pneumolysin release (Gonzalez-Juarbe et al, 2020; Mina & Klugman, 2014; A. L. Richard, Siegel, Erikson, & Weiser, 2014). Many of these published studies focused primarily on Spn specific colonization, transmission, and pathogenesis, and do not explore the impact of Spn on IAV binding, replication, or dissemination.…”

Section: Introductionmentioning

confidence: 99%

Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus

et al. 2020

Preprint

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Secondary bacterial infection, especially with Streptococcus pneumoniae (Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naïve recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one.SignificanceAirborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection with Streptococcus pneumoniae reduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.

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Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial Toxin-Mediated Necroptosis

Cited by 4 publications

References 0 publications

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

Microbiota Modulating Nutritional Approaches to Countering the Effects of Viral Respiratory Infections Including SARS-CoV-2 through Promoting Metabolic and Immune Fitness with Probiotics and Plant Bioactives

Management of Severe Influenza

Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus

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