1. High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures
- Author
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El-ad David Amir, Ana Fernandez-Sesma, Irene Ramos, Dabeiba Bernal-Rubio, Uma Potla, Ignacio Mena, Theodore R. Pak, Andrew Kasarskis, Kevin Maringer, Ana M. Maestre, Anthony C. Fredericks, Adeeb Rahman, Rebecca E. Hamlin, and Miriam Merad
- Subjects
0301 basic medicine ,Innate immune system ,Secondary infection ,viruses ,030231 tropical medicine ,virus diseases ,General Medicine ,Dengue virus ,Biology ,biochemical phenomena, metabolism, and nutrition ,medicine.disease_cause ,Virology ,Virus ,Proinflammatory cytokine ,Pathogenesis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Immunology ,medicine ,Mass cytometry ,Research Article - 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.
- Published
- 2017