Type III interferon(IFN-L) as a potential drug in SARS-CoV2 infection: Evaluation of antiviral and immune modulatory effects in a human in vitro model

  • Funded by Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
  • Total publications:0 publications

Grant number: 01KI20182

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2020
  • Known Financial Commitments (USD)

    $256,732.71
  • Funder

    Bundesministerium für Bildung und Forschung [German Federal Ministry of Education and Research] (BMBF)
  • Principle Investigator

    Pending
  • Research Location

    Germany, Europe
  • Lead Research Institution

    Helmholtz Zentrum für Infektionsforschung mbH, Braunschweig
  • Research Category

    Therapeutics research, development and implementation

  • Research Subcategory

    Pre-clinical studies

  • Special Interest Tags

    Gender

  • Study Subject

    N/A

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

discovery - Clinical courses of infections with severe acute respiratory syndrome coronavirus (SARS-CoV2) are characterized by viral replication in lung epithelial cells. Infection is accompanied with the activation of early innate immune reactions, in particular the induction of type I interferons (IFN-a/ß) and type III IFN (IFN-lambda). These IFNs are a group of cytokines that strongly restrict viral replication but have pronounced, albeit differential immune modulatory activities. Thereby, they not only control infections but they induce the secretion of inflammatory cytokines from infiltrating immune cells. In the severe courses of disease, these overshooting inflammatory reactions represent one of the most critical clinical phenotypes, which often cause the hardly controllable pathological consequences of the infection. Due to a restricted cell target spectrum of type III IFNs the proinflammatory site effects of type I IFNs are strongly reduced and might thus offer an opportunity for specific treatment. This project aims at elucidating the potential benefit of type III IFN in treating SARS-CoV2 infections. An advanced cell co-culture model based on human epithelial cells and human iPS cell-derived macrophages will be used to elucidate the antiviral properties as well as the immune modulatory consequences of IFN-lambda. Single cell RNA sequencing will determine viral replication, epithelial cell death vs tissue repair as well as the activation profile of macrophages, i.e. their pro-inflammatory vs. anti-inflammatory phenotype.