ArticlePLoS pathogens2021
Sequential targeting of interferon pathways for increased host resistance to bacterial superinfection during influenza.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- SARS-CoV-2-International journal of microbiology · 2026Review
- Hyperinflammation and immunomodulation in influenza, SARS-CoV-2 and syncytial respiratory virus infection in adults: from innate immune responses and biomarkers to clinical and therapeutic implications.Frontiers in microbiology · 2026Review
- Myeloid cell expression of the VDR and parathyroid hormone control the host response to influenza infection in mice.Frontiers in immunology · 2026Article
- Editorial: Immune correlates of protection: Insight into microbial co-infection with special emphasis on influenza-Frontiers in immunology · 2025Article
- Post-influenza bacterial infection: mechanisms of pathogenesis and advances in therapeutic strategies.Frontiers in microbiology · 2025Review
- Article
- Human monoclonal antibodies protect against viral-mediated pneumococcal superinfection.Frontiers in immunology · 2024Article
- The Activation of the RIG-I/MDA5 Signaling Pathway upon Influenza D Virus Infection Impairs the Pulmonary Proinflammatory Response Triggered by Mycoplasma bovis Superinfection.Journal of virology · 2023Article
- Synergistic Protection against Secondary Pneumococcal Infection by Human Monoclonal Antibodies Targeting Distinct Epitopes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Type I IFN Signaling Is Essential for Preventing IFN-γ Hyperproduction and Subsequent Deterioration of Antibacterial Immunity during Postinfluenza Pneumococcal Infection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination.JCI insight · 2022Article
- Disease Tolerance during Viral-Bacterial Co-Infections.Viruses · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Bacterial co-infections represent a major clinical complication of influenza. Host-derived interferon (IFN) increases susceptibility to bacterial infections following influenza, but the relative roles of type-I versus type-II IFN remain poorly understood. We have used novel mouse models of co-infection in which colonizing pneumococci were inoculated into the upper respiratory tract; subsequent sublethal influenza virus infection caused the bacteria to enter the lungs and mediate lethal disease. Compared to wild-type mice or mice deficient in only one pathway, mice lacking both IFN pathways demonstrated the least amount of lung tissue damage and mortality following pneumococcal-influenza virus superinfection. Therapeutic neutralization of both type-I and type-II IFN pathways similarly provided optimal protection to co-infected wild-type mice. The most effective treatment regimen was staggered neutralization of the type-I IFN pathway early during co-infection combined with later neutralization of type-II IFN, which was consistent with the expression and reported activities of these IFNs during superinfection. These results are the first to directly compare the activities of type-I and type-II IFN during superinfection and provide new insights into potential host-directed targets for treatment of secondary bacterial infections during influenza.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.