TY - JOUR AU - Hamlin, Rebecca E. AU - Rahman, Adeeb AU - Pak, Theodore R. AU - Maringer, Kevin AU - Mena, Ignacio AU - Bernal-Rubio, Dabeiba AU - Potla, Uma AU - Maestre, Ana M. AU - Fredericks, Anthony C. AU - Amir, El-ad D. AU - Kasarskis, Andrew AU - Ramos, Irene AU - Merad, Miriam AU - Fernandez-Sesma, Ana T1 - High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures PY - 2017/09/15/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.92424 VL - 2 IS - 13 UR - https://doi.org/10.1172/jci.insight.92424 PB - The American Society for Clinical Investigation ER -