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

Vinit Upasani, Carolina Scagnolari, Federica Frasca, Nikaia Smith, Vincent Bondet, Axelle Vanderlinden, Sokchea Lay, Heidi Auerswald, Sothy Heng, Denis Laurent, Sowath Ly, Veasna Duong, Guido Antonelli, Philippe Dussart, Darragh Duffy, Tineke Cantaert*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    7 Citations (Scopus)
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    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 IFN alpha 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.

    Original languageEnglish
    Article number605087
    Number of pages12
    JournalFrontiers in Immunology
    Volume11
    DOIs
    Publication statusPublished - 17-Dec-2020

    Keywords

    • dengue virus
    • plasmacytoid dendritic cell
    • myloid dendritic cells
    • interferon stimulated genes
    • simoa immunoassay
    • type I interferon
    • VIRUS-INFECTION REQUIRES
    • IFN-BETA
    • HEMORRHAGIC-FEVER
    • B-CELLS
    • POSTTRANSCRIPTIONAL REGULATION
    • RECEPTOR IFNAR-2
    • RESPONSES
    • ALPHA
    • DISEASE
    • ENHANCEMENT

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