The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
Influenza Infection Leads to Increased Susceptibility to Subsequent Bacterial Superinfection by Impairing NK Cell Responses in the Lung
Open accessAbstract
Influenza viral infection is well-known to predispose to subsequent bacterial superinfection in the lung but the mechanisms have remained poorly defined. We have established a murine model of heterologous infections by an H1N1 influenza virus and Staphylococcus aureus. We found that indeed prior influenza infection markedly increased the susceptibility of mice to secondary S. aureus superinfection. Severe sickness and heightened bacterial infection in flu and S. aureus dual-infected animals were associated with severe immunopathology in the lung. We further found that flu-experienced lungs had an impaired NK cell response in the airway to subsequent S. aureus bacterial infection. Thus, adoptive transfer of naive NK cells to the airway of prior flu-infected mice restored flu-impaired antibacterial host defense. We identified that TNF-alpha production of NK cells played an important role in NK cell-mediated antibacterial host defense as NK cells in flu-experienced lungs had reduced TNF-alpha expression and adoptive transfer of TNF-alpha-deficient NK cells to the airway of flu-infected mice failed to restore flu-impaired antibacterial host defense. Defected NK cell function was found to be an upstream mechanism of depressed antibacterial activities by alveolar macrophages as contrast to naive wild-type NK cells, the NK cells from flu-infected or TNF-alpha-deficient mice failed to enhance S. aureus phagocytosis by alveolar macrophages. Together, our study identifies the weakened NK cell response in the lung to be a novel critical mechanism for flu-mediated susceptibility to bacterial superinfection.
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In the citing paper
“may occur shortly after influenza virus has been largely cleared from the lungs, when the host appears to be more susceptible to bacterial infection”
From Bacterial and viral infections associated with influenza (2013) · cites this paper as [1]
In the citing paper
“Bacterial infection may be concurrent with influenza viral infection, and the resulting co‐infection can lead to an enhanced pneumonic illness or may occur shortly after influenza virus has been largely cleared from the lungs”
From Bacterial and viral infections associated with influenza (2013) · cites this paper as [1]
In the citing paper
“the resulting co‐infection can lead to an enhanced pneumonic illness”
From Bacterial and viral infections associated with influenza (2013) · cites this paper as [1]
In the citing paper
“our results suggest that alteration of macrophage function alone through a natural killer cell-mediated mechanism is not sufficient to explain increased susceptibility to S. aureus.”
From Influenza virus primes mice for pneumonia from Staphylococcus aureus. (2011) · cites this paper as [46]
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Metadata
- Authors
- Small, C.-L., Shaler, C. R., McCormick, S., Jeyanathan, M., Damjanovic, D., Brown, E. G., Arck, P., Jordana, M., Kaushic, C., Ashkar, A. A., & Xing, Z.
- Affiliations
- Michael G. DeGroote Institute for Infectious Disease Research (CA)
- University of Ottawa (CA)
- McMaster University (CA)
- Corresponding author
- McCormick, Sarah
- Jeyanathan, Mangalakumari
- Damjanovic, Daniela
- Jordana, Manel
- Kaushic, Charu
- Xing, Zhou
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-01-18
- Volume
- 184
- Issue
- 4
- Pages
- 2048-2056
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2122758441
- Cited by
- 216
- References
- 41
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 17 · 2020: 14 · 2019: 12 · 2018: 10 · 2017: 14 · 2016: 17 · 2015: 17 · 2014: 18 · 2013: 25 · 2012: 10
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- influenza virus, secondary bacterial infection, Staphylococcus aureus, natural killer cells, TNF-α, alveolar macrophages, secondary infection susceptibility, heterologous infection, lung immunopathology, phagocytosis, adoptive transfer, H1N1 influenza
- MeSH terms
- Animals, Disease Susceptibility, Female, Killer Cells, Natural, Mice, Inbred C57BL, Orthomyxoviridae Infections, Pneumonia, Viral, Staphylococcal Infections, Superinfection, Macrophages, Alveolar, Pneumonia, Bacterial, Mice, Influenza A Virus, H1N1 Subtype
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