ArticleThe Journal of clinical investigation2020
Respiratory syncytial virus infection exacerbates pneumococcal pneumonia via Gas6/Axl-mediated macrophage polarization.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Respiratory and Gut Microbiome Modification during Respiratory Syncytial Virus Infection: A Systematic Review.Viruses · 2024Pooled it
- An Appraisal of the Potential Downstream Benefits of RSV Vaccination in Older Adults.Reviews in medical virology · 2026Review
- Biomimetic nanodelivery of antagomiR-155-5p ameliorates wear particle-induced osteolysis by dual regulation of Gas6/Axl-mediated macrophage inflammation.Journal of orthopaedic translation · 2026Article
- Live nontypeable Haemophilus influenzae exacerbates respiratory syncytial virus-associated lower airway inflammation.Respiratory research · 2026Article
- Integrated Transcriptomics Reveals Evolutionary Trajectories and Cell Density-Dependent Mechanisms in Aldosterone-Producing Adenomas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Macrophage Immune Responses in Viral Infections: Functional Plasticity and Therapeutic Targeting.Journal of microbiology and biotechnology · 2026Review
- TLR7/8 signaling balances cytokine responses in neonatal monocytes.Scientific reports · 2026Article
- Association between seasonal respiratory virus activity and invasive pneumococcal disease in central Ontario, Canada.BMC infectious diseases · 2026Article
- Attenuation of canine distemper virus leads to a potent antiviral innate immune response with restricted infection of alveolar macrophages.Journal of virology · 2026Article
- Gas6/Axl-mediated macrophage hyporesponsiveness drives severe pulmonary mucormycosis in diabetic mice.Frontiers in cellular and infection microbiology · 2026Article
- Multi-dimensional epidemiology of pediatric acute respiratory tract infection in Ningbo, China (2020-2024): age-specific susceptibility, pathogen dynamics, and epidemiological trends.Frontiers in cellular and infection microbiology · 2026Article
- Single-cell transcriptomics reveals dynamic reprogramming of testicular immunity inZoological research · 2025Article
- RSV: an overview of infection in adults.Pneumonia (Nathan Qld.) · 2025Review
- Temporal Changes in Nasopharyngeal Pneumococcal Colonization Density Associated With Respiratory Syncytial Virus and Influenza in a South African Household Cohort Study, 2016-2018.Open forum infectious diseases · 2025Article
- Monitoring Macrophage Polarization in Infectious Disease, Lesson From SARS-CoV-2 Infection.Reviews in medical virology · 2025Review
- Exploring Ribosomal Genes as Potential Biomarkers of the Immune Microenvironment in Respiratory Syncytial Virus Infection.Biochemical genetics · 2025Article
- Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.International journal of molecular sciences · 2025Review
- Article
- Cordycepin, lactoferrin, and Sargassum fusiforme polysaccharides protects against RSV via M2-like macrophage polarization.Frontiers in immunology · 2025Article
- Lower respiratory tract co-infection ofFrontiers in cellular and infection microbiology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with respiratory syncytial virus (RSV) infection exhibit enhanced susceptibility to subsequent pneumococcal infections. However, the underlying mechanisms involved in this increased susceptibility remain unclear. Here, we identified potentially novel cellular and molecular cascades triggered by RSV infection to exacerbate secondary pneumococcal pneumonia. RSV infection stimulated the local production of growth arrest-specific 6 (Gas6). The Gas6 receptor Axl was crucial for attenuating pneumococcal immunity in that the Gas6/Axl blockade fully restored antibacterial immunity. Mechanistically, Gas6/Axl interaction regulated the conversion of alveolar macrophages from an antibacterial phenotype to an M2-like phenotype that did not exhibit antibacterial activity, and the attenuation of caspase-1 activation and IL-18 production in response to pneumococcal infection. The attenuated IL-18 production failed to drive both NK cell-mediated IFN-γ production and local NO and TNF-α production, which impair the control of bacterial infection. Hence, the RSV-mediated Gas6/Axl activity attenuates the macrophage-mediated protection against pneumococcal infection. The Gas6/Axl axis could be a potentially novel therapeutic target for RSV-associated secondary bacterial infection.
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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.