Influenza Virus Primes Mice for Pneumonia From Staphylococcus aureus

Iverson, Amy; Boyd, Kelli L.; McAuley, Julie; Plano, Lisa R. W.; Hart, Mark E.; McCullers, Jonathan A.

doi:10.1093/infdis/jiq113

Cited by 154 publications

(160 citation statements)

References 46 publications

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“…In an animal study of co-infected mice, similar to the data reported by McCullers using co-infected mouse models [15][16][17], we observed pathological changes accompanied by pulmonary alveolar hemorrhage in addition to a significantly decreased survival rate [18]. Influenza virus or S. pneumoniae infection alone induced moderate pneumonia, whereas co-infected mice showed severe bronchopneumonia with massive hemorrhage, resulting in death of these mice two days after inoculation with S. pneumoniae.…”

Section: Related Molecules Referencessupporting

confidence: 87%

Mechanisms of Increased Severity of Influenza-Related Pneumonia

Seki¹

2013

General Med

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Influenza-related pneumonia is an important complication of influenza, and it has been suggested that excessive inflammatory reactions, including "cytokine storm", may contribute to the mechanisms underlying severe pneumonia. Human data and mice co-infected with influenza virus and Streptococcus pneumoniae show increased severity of illness according to the elevation of cytokines/chemokines, and mice with genetic knock-out of immune molecules such as Toll-like receptor 3 and IRAK-M also show hyper-immune responses and reduced survival following influenza virus infection. Such findings suggest that innate immune responses and excessive neutrophil activation might be related to severe inflammatory changes in the lungs, and immunomudulatory therapy may thus be effective against severe influenza-related pneumonia.

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Section: Related Molecules Referencessupporting

confidence: 87%

Mechanisms of Increased Severity of Influenza-Related Pneumonia

Seki¹

2013

General Med

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“…Overall, the immunosuppressive effect of NS1 extend to the expression of multiple cytokines, likely contributing not only to impaired viral clearance, but also to impaired responses to unrelated pathogens (Fernandez-Sesma et al, 2006). Additionally, the genome of most influenza A isolates codes for the accessory protein PB1-F2, a cytotoxin that worsens the outcome of secondary bacterial infections with S. aureus and S. pneumoniae (Iverson et al, 2011;McAuley et al, 2007).…”

Section: Other Mechanismsmentioning

confidence: 99%

Viral–bacterial interactions in the respiratory tract

Bellinghausen

Rohde

Savelkoul

et al. 2016

Journal of General Virology

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“…Subsequent studies found that influenza infection predisposes an animal to a more severe pneumococcal infection [9]. The viral-bacterial interaction is not limited to influenza and S. pneumoniae: similar interactions have been noted between human metapneumovirus and S. pneumoniae [10] and between influenza and S. aureus [11][12][13].…”

mentioning

confidence: 86%

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza andStreptococcus pneumoniae

Shrestha

Foxman

Dawid

et al. 2013

J. R. Soc. Interface.

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A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immunemediated model of the viral -bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4-6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness.

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Influenza Virus Primes Mice for Pneumonia From Staphylococcus aureus

Cited by 154 publications

References 46 publications

Mechanisms of Increased Severity of Influenza-Related Pneumonia

Mechanisms of Increased Severity of Influenza-Related Pneumonia

Viral–bacterial interactions in the respiratory tract

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza andStreptococcus pneumoniae

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