%0 Journal Article
%T Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
%A Anita Desai
%A Anna Malawista
%A Bram Gerritsen
%A Brent Vander Wyk
%A David van Dijk
%A Erol Fikrig
%A Jayasree Sivadasan
%A Kevin Moon
%A Mahesh M. Kumar
%A Manjunatha M. Venkataswamy
%A Matthew Amodio
%A Megan E. Cahill
%A Monique M. Richards
%A Priti Kumar
%A Ruth R. Montgomery
%A Smita Krishnaswamy
%A Steven H. Kleinstein
%A Vasanthapuram Ravi
%A Xiaomei Wang
%A Yujiao Zhao
%J -
%D 2020
%R 10.1371/journal.pntd.0008112
%X The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFN¦Â were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection
%K Zika virus
%K Dengue virus
%K Immune response
%K T cells
%K Dengue fever
%K Cytokines
%K Cytotoxic T cells
%K Immune cells
%U https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008112