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

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.

Differential effects of orally administered <i>Lactobacillus acidophilus</i> L-55 on the gene expression of cytokines and master immune switches in the ileum and spleen of laying hen with an attenuated Newcastle disease virus vaccine

“…2a and 2b). The reduced expression of type I IFN observed as a result of the administration of high doses of LaL-55 may have occurred to avoid excessive downmodulation of the immune response in the negative feedback loop [37]. The results of this study may require further investigation of the appropriate doses and methods of administration for LaL-55.…”

Differential levels of IFNα subtypes in autoimmunity and viral infection

“…13 , Reynolds et al (LEAP cohort) 16 , Bost et al (In review) (ASSESS cohort), Menon et al . (In preparation), Sultanik et al 117 (C10-08 cohort) and Upasani et al 18 .…”

“…The Upasani et al 18 cohort includes 115 children (≥ 2 years) who presented with dengue-like symptoms at the Kanta Bopha Hospital in Phnom Penh, Cambodia. Blood samples were obtained within 96 h of fever onset at hospital admittance.…”

“…The dengue cohort of this paper includes 56 of these 115 patients, randomly selected. The dengue cohort and the Upasani et al 18 cohort are not statistically different in terms of age (10, IQR 6-12 vs 9, IQR 5-11) and pan-alpha interferon concentrations (p=0.536, Mann-Whitney test), and these two cohorts show similar percentages of female (48% vs 53), DF (82% vs 72), DHF (13% vs 17), DSS (5% vs 9), primary infection (25% vs 17) or secondary infection (75% vs 71) patients.…”

Viral-Induced Inflammatory Coagulation Disorders: Preparing for Another Epidemic

“…In viral hemorrhagic fevers, pathogens infect and replicate within these antigen-presenting and cytokine-producing cells and then disseminate rapidly within various host cell types. Viral dissemination is aided by the suppression of type I IFN responses due to the myeloid dendritic cell malfunction [46]. Infected dendritic cells are impaired, and the loss of their appropriate function can lead to lymphocytic apoptosis and excess other types of lymphocyte cell death, findings that are linked to fatality.…”