Decreased Type I Interferon Production by Plasmacytoid Dendritic Cells Contributes to Severe Dengue - Institut Pasteur Access content directly
Journal Articles Frontiers in Immunology Year : 2020

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

Veasna Duong
Philippe Dussart

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.
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pasteur-03245784 , version 1 (02-06-2021)

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Vinit Upasani, Carolina Scagnolari, Federica Frasca, Nikaïa Smith, Vincent Bondet, et al.. Decreased Type I Interferon Production by Plasmacytoid Dendritic Cells Contributes to Severe Dengue. Frontiers in Immunology, 2020, 11, pp.605087. ⟨10.3389/fimmu.2020.605087⟩. ⟨pasteur-03245784⟩
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