Literature DB >> 28679950

High-dimensional CyTOF analysis of dengue virus-infected human DCs reveals distinct viral signatures.

Rebecca E Hamlin1,2, Adeeb Rahman3,4, Theodore R Pak2,4,5, Kevin Maringer1,6, Ignacio Mena1, Dabeiba Bernal-Rubio1, Uma Potla1, Ana M Maestre1, Anthony C Fredericks1,2, El-Ad D Amir3,7, Andrew Kasarskis2,4,5, Irene Ramos1, Miriam Merad2,3,7, Ana Fernandez-Sesma1,2.   

Abstract

Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human DCs, the initial targets of primary infections that likely affect infection outcomes. Strikingly, DENV-4 replication peaked earlier and promoted stronger innate immune responses, with increased expression of DC activation and migration markers and increased cytokine production, compared with DENV-2. In addition, infected DCs produced higher levels of inflammatory cytokines compared with bystander DCs, which mainly produced IFN-induced cytokines. These high-dimensional analyses during DENV-2 and DENV-4 infections revealed distinct viral signatures marked by different replication strategies and antiviral innate immune induction in DCs, which may result in different viral fitness, transmission, and pathogenesis.

Entities:  

Keywords:  Cytokines; Dendritic cells; Immunology; Innate immunity; Virology

Year:  2017        PMID: 28679950      PMCID: PMC5499363          DOI: 10.1172/jci.insight.92424

Source DB:  PubMed          Journal:  JCI Insight        ISSN: 2379-3708


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