{
  "abstract": "Background Individuals with asthma have increased susceptibility to bacterial pneumonia, potentially related to altered mucosal immunity and corticosteroid therapy. Cross-sectional studies suggest higher rates of Streptococcus pneumoniae (pneumococcus) carriage in asthma, but the dynamics of colonisation and mucosal immune mechanisms remain unclear.Methods We assessed 50 participants with well-controlled asthma (on moderate inhaled corticosteroid therapy) and 151 healthy controls, all experimentally challenged with type 6B pneumococcus. A subset of asthma participants (n=12) who became colonised were rechallenged 6-11 months later with the same pneumococcal isolate. Colonisation rates (from nasal wash), systemic antibody levels and mucosal cellular and cytokine responses were compared between groups.Results The colonisation rates were 56% (28/50) in asthma participants and 45% (68/151) in controls (p=0.17). The median duration of colonisation was shorter in asthma participants (14 days, IQR 7–29) compared with controls (29 days, IQR 14–29, p=0.034), although bacterial densities were similar between both groups. Despite an increase in pneumococcus-capsule-specific antibodies following colonisation, 4/12 asthma participants were recolonised after rechallenge. Nasal neutrophil and T cell frequencies, particularly mucosa-associated invariant T cells, were lower in asthma participants compared with healthy controls before challenge. Similarly, 22 out of 30 measured mucosal cytokines were significantly lower at baseline in asthma participants. Despite these deficits, both groups exhibited similar recruitment of monocytes and granulocytes to the nasal mucosa following colonisation.Conclusions Adults with asthma demonstrate reduced mucosal immune tone and impaired development of protection against pneumococcal recolonisation, despite preserved innate recruitment and generation of pneumococcal-specific antibodies. These findings identify distinct mucosal immune alterations in asthma that may underlie persistent susceptibility to pneumococcal infection and inform strategies for targeted vaccination and immune modulation.Trial registration number ISRCTN16755478.",
  "authors": [
    {
      "affiliations": [
        "NIHR Oxford Biomedical Research Centre, Oxford Vaccine Group, University of Oxford, Oxford, UK",
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain"
      ],
      "name": "Jesús Reiné"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Seher Raza Zaidi"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Center for Infectious Diseases, Leiden University, Leiden University Medical Center, Leiden, Netherlands"
      ],
      "name": "Simon P Jochems"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Sherin Pojar"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Elissavet Nikolaou"
    },
    {
      "affiliations": [
        "NIHR Oxford Biomedical Research Centre, Oxford Vaccine Group, University of Oxford, Oxford, UK",
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Elena Mitsi"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Esther L German"
    },
    {
      "affiliations": [
        "Research Department of Infection, Division of Infection and Immunity, University College London, London, UK",
        "Biomedical and Life Sciences, Lancaster University, Lancaster, UK"
      ],
      "name": "Caroline M Weight"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Angela D Hyder-Wright"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Hugh Adler"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Helen Hill"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Caroline Hales"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK"
      ],
      "name": "Victoria Connor"
    },
    {
      "affiliations": [
        "NIHR Oxford Biomedical Research Centre, Oxford Vaccine Group, University of Oxford, Oxford, UK",
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Carla Solórzano"
    },
    {
      "affiliations": [
        "Research Department of Infection, Division of Infection and Immunity, University College London, London, UK"
      ],
      "name": "Robert S Heyderman"
    },
    {
      "affiliations": [
        "Medical School, Curtin University, Perth, Western Australia, Australia"
      ],
      "name": "John D Blakey"
    },
    {
      "affiliations": [
        "Institute for Child Health, University College London, London, UK"
      ],
      "name": "David Goldblatt"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi",
        "Institute of Regeneration and Repair, College of Medicine and Veterinary Medicine, University of Edinburgh Division of Clinical and Surgical Sciences, Edinburgh, UK"
      ],
      "name": "Stephen B Gordon"
    },
    {
      "affiliations": [
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK",
        "Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK",
        "Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"
      ],
      "name": "Jamie Rylance"
    },
    {
      "affiliations": [
        "NIHR Oxford Biomedical Research Centre, Oxford Vaccine Group, University of Oxford, Oxford, UK",
        "Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK"
      ],
      "name": "Daniela M Ferreira"
    }
  ],
  "title": "Pneumococcal colonisation and mucosal immunity in adults with asthma following experimental human challenge",
  "uid": "32ca911d-f447-5254-9405-512b1913345f"
}