{
  "abstract": "Introduction Mitochondrial antiviral signalling protein (MAVS), a 540-amino acid protein primarily located on the mitochondria outer membrane plays a pivotal role in antiviral immunity as an intracellular pathogen recognition receptor for viruses, inducing type I/III IFN and activating NFκB and IRF3. Recent findings implicate MAVS signalling also in antifungal immune responses. However, the role of MAVS in antibacterial host defence remains unknown. The Gram-negative bacterium non-typeable Haemophilus influenzae (NTHi) is the predominant pathogen in airways diseases such as asthma and chronic obstructive pulmonary disease. We aimed to determine the role of MAVS in immune defence against NTHi in vivo.Methods We infected C57BL/6 (wt) and MAVS KO mice with NTHi and analysed bacterial loads, weight loss, pathological change of lung tissues, infection progression, inflammatory and immune responses by transcriptomics and spectral flow cytometry.Results NTHi infection leads to the degradation of MAVS. MAVS deficiency results in compromised bacterial control during NTHi infection. Mavs -/- mice demonstrated impaired early production of many proinflammatory cytokines including a weaker induction of IFN-β and reduced accumulation and activation of NK cells. Depletion of macrophages eliminated the disparity in bacterial loads and weight loss between the two mouse strains. Moreover, in vitro experiments using freshly isolated alveolar macrophages revealed that MAVS played an important role in macrophage function against bacterial infections by detecting bacterial RNA.Conclusions We have discovered an important new role for MAVS in early innate immunity against bacterial lung infection, both in vitro and in vivo.",
  "authors": [
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "Y Long"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "SB Morgan"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "Y Mai"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "P Klenerman"
    },
    {
      "affiliations": [
        "University of Oxford, Oxford, UK"
      ],
      "name": "TSC Hinks"
    }
  ],
  "title": "S61 Protective early innate immune activation by mitochondrial antiviral signalling protein (MAVS) in bacterial pneumonia",
  "uid": "9935b1b4-141a-5587-a34a-ac4a1db77004"
}