Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures
Rebecca E. Hamlin, Adeeb Rahman, Theodore R. Pak, Kevin Maringer, Ignacio Mena, Dabeiba Bernal-Rubio, Uma Potla, Ana M. Maestre, Anthony C. Fredericks, El-ad D. Amir, Andrew Kasarskis, Irene Ramos, Miriam Merad, Ana Fernandez-Sesma
Rebecca E. Hamlin, Adeeb Rahman, Theodore R. Pak, Kevin Maringer, Ignacio Mena, Dabeiba Bernal-Rubio, Uma Potla, Ana M. Maestre, Anthony C. Fredericks, El-ad D. Amir, Andrew Kasarskis, Irene Ramos, Miriam Merad, Ana Fernandez-Sesma
View: Text | PDF
Research Article Immunology Virology

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

  • Text
  • PDF
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.

Authors

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

×

Figure 2

Comparing cellular marker positivity during mock, DENV-2, and DENV-4 infections by autogating.

Options: View larger image (or click on image) Download as PowerPoint
Comparing cellular marker positivity during mock, DENV-2, and DENV-4 inf...
Heat maps comparing cellular marker positivity by denoting cells as either positive or negative for each marker during mock, dengue virus 2 (DENV-2), and DENV-4 infections. For all plots, markers are ordered vertically by hierarchical clustering of the rows, which places markers with similar expression profiles closer together. Statistical significance was determined using a 2-sided Fisher’s exact test at a threshold of α = 10–5 with Bonferroni correction for multiple testing. Cellular markers not representing a significant difference between infection conditions at this threshold are labeled with “NS”; all others are significant. Calculations were made using the event counts from mass cytometry by time-of-flight (CyTOF) data, as determined by autogating of cells positive for each marker based on the 99th percentile threshold, which was set for mock treatment at 8 hours after infection (hpi). The comparative effects on each marker were calculated as the log10 of the relative risk for positive marker frequency between the indicated infection conditions. The histograms within the heat map color scales show the total number of cells matching that intensity range, revealing the overall distribution of the values. One representative DC donor of seven is shown. (A) DENV-2 infection and mock treatment are compared. Red indicates greater marker expression during DENV-2 infection, and blue indicates greater marker expression during mock treatment. (B) DENV-4 infection and mock treatment are compared. Red indicates greater marker expression during DENV-4 infection, and blue indicates greater marker expression during mock treatment. (C) DENV-4 and DENV-2 infections are compared. Red indicates greater marker expression during DENV-4 infection, and blue indicates greater marker expression during DENV-2 infection. White indicates no difference in marker expression between the infection conditions.

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts