Decreased Type I Interferon Production by Plasmacytoid Dendritic Cells Contributes to Severe Dengue

Front Immunol. 2020 Dec 17;11:605087. doi: 10.3389/fimmu.2020.605087. eCollection 2020.

Abstract

The clinical presentation of dengue virus (DENV) infection is variable. Severe complications mainly result from exacerbated immune responses. Type I interferons (IFN-I) are important in antiviral responses and form a crucial link between innate and adaptive immunity. Their contribution to host defense during DENV infection remains under-studied, as direct quantification of IFN-I is challenging. We combined ultra-sensitive single-molecule array (Simoa) digital ELISA with IFN-I gene expression to elucidate the role of IFN-I in a well-characterized cohort of hospitalized Cambodian children undergoing acute DENV infection. Higher concentrations of type I IFN proteins were observed in blood of DENV patients, compared to healthy donors, and correlated with viral load. Stratifying patients for disease severity, we found a decreased expression of IFN-I in patients with a more severe clinical outcome, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This was seen in parallel to a correlation between low IFNα protein concentrations and decreased platelet counts. Type I IFNs concentrations were correlated to frequencies of plasmacytoid DCs, not DENV-infected myloid DCs and correlated inversely with neutralizing anti-DENV antibody titers. Hence, type I IFN produced in the acute phase of infection is associated with less severe outcome of dengue disease.

Keywords: dengue virus; interferon stimulated genes; myloid dendritic cells; plasmacytoid dendritic cell; simoa immunoassay; type I interferon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Cambodia
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Dengue / blood
  • Dengue / diagnosis
  • Dengue / immunology
  • Dengue / virology*
  • Dengue Virus / immunology
  • Dengue Virus / pathogenicity*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Interferon Type I / blood*
  • Interferon Type I / genetics
  • Male
  • Platelet Count
  • Prognosis
  • Severity of Illness Index
  • Single Molecule Imaging
  • Time Factors
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Interferon Type I