Pneumococcal conjugate vaccine modulates macrophage-mediated innate immunity in pneumonia caused by Streptococcus pneumoniae following influenza |
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| Affiliation: | 1. Department of Microbiology and Infectious Diseases, Faculty of Medicine, Toho University Graduate School of Medicine, Tokyo, 143-8540, Japan;2. First Department of Internal Medicine, Hokkaido University Hospital, Hokkaido, 060-8638, Japan;3. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48105, USA;4. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48105, USA;1. Department of Biomedical and Clinical Sciences ‘L. Sacco’, University of Milan, Milan, Italy;2. Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia;1. Department of Public Health and Pediatric Sciences, University of Turin, Medical School, Turin, Italy;2. Department of Pediatrics, Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy;1. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia;2. Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh;3. Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns & Townsville, Queensland, Australia;4. College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia;5. University of New England, New South Wales, Australia |
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| Abstract: | Pneumococcal conjugate vaccination (PCV) may prevent influenza-related pneumonia, including Streptococcus pneumoniae pneumonia. To investigate PCV efficacy against secondary pneumococcal pneumonia following influenza, PCV was administered intramuscularly 2 and 5 weeks before S. pneumoniae serotype-3 colonization of murine nasopharynges followed by intranasal challenge with a sublethal dose of influenza A virus. Bacterial and viral loads, including innate immune responses were compared across conditions. PCV vaccination improved the survival of mice with secondary pneumococcal pneumonia and significantly reduced the pulmonary bacterial burden. Increased monocyte/macrophage influx into the lungs, alleviated loss of alveolar macrophages and decreased neutrophil influx into the lungs occurred in PCV-treated mice irrespective of pneumococcal colonization. Higher monocyte chemoattractant protein 1 levels and lower levels of CXCL1, interferon-γ, interleukin-17A, and IL-10, were detected in PCV-treated mice. Additionally, PCV treatment activated the macrophage intracellular killing of S. pneumoniae. Collectively, PCV potentially modulates the host’s innate immunity and specific antibodies induction. Macrophage-related innate immunity should be further explored to elucidate the efficacy and mechanisms of PCV versus influenza-related life-threatening diseases. |
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| Keywords: | Pneumococcal conjugate vaccine Pneumococcal colonization Influenza virus infection Secondary pneumococcal pneumonia Innate immunity Monocyte/macrophages |
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