Social network architecture of human immune cells in ZIKV-infected patients highlights a unique role of plasmacytoid dendritic cells

Zika virus (ZIKV) is an emerging mosquito-borne pathogen with increasing public health significance. To characterize interconnected immune responses to ZIKV, we here examined transcriptional signatures of CD4 and CD8 T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with naturally-acquired ZIKV infection. While gene expression patterns from most cell subsets displayed signs of impaired antiviral immune activity, pDCs showed a highly distinct transcriptional response marked by an activation of innate immune recognition and type I interferon signaling pathways, combined with a downregulation of key host factors known to support ZIKV replication steps. At the same time, pDCs exhibited a unique expression pattern of gene modules that were tightly correlated with alternative cell populations, suggesting highly collaborative interactions between pDCs and other immune cells. Together, these results point towards a discrete but integrative role of pDCs in the human immune response to ZIKV infection. Overall design: 3 ZIKV infected patients and 3 age and gender matched healthy donors were used as control, in addition, we also performed cell subsets analysis of 3 healthy donor infected with ZIKV in vitro.