Portal de Periódicos da CAPES

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

2017; American Society for Clinical Investigation; Volume: 2; Issue: 13 Linguagem: Inglês

10.1172/jci.insight.92424

2379-3708

Rebecca E. Hamlin, Adeeb Rahman, Theodore Pak, Kevin Maringer, Ignacio Mena, Dabeiba Bernal‐Rubio, Uma Potla, Ana M. Maestre, Anthony C. Fredericks, El-ad David Amir, Andrew Kasarskis, Irene Ramos, Miriam Mérad, Ana Fernandez‐Sesma,

Insect symbiosis and bacterial influences

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.