Abstract
Zika virus (ZIKV) is a mosquito-borne pathogen with increasing public health significance. To characterize immune responses to ZIKV, here we examine transcriptional signatures of CD4 T, CD8 T, B, and NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with ZIKV infection. While gene expression patterns from most cell subsets display signs of impaired antiviral immune activity, pDCs from infected host have distinct transcriptional response associated with activation of innate immune recognition and type I interferon signaling pathways, but downregulation of key host factors known to support ZIKV replication steps; meanwhile, pDCs exhibit a unique expression pattern of gene modules that are correlated with alternative cell populations, suggesting collaborative interactions between pDCs and other immune cells, particularly B cells. Together, these results point towards a discrete but integrative function of pDCs in the human immune responses to ZIKV infection.
Highlights
Zika virus (ZIKV) is a mosquito-borne pathogen with increasing public health significance
Our previous studies demonstrated that in individuals with naturally acquired ZIKV infection, ZIKV RNA was detectable in myeloid dendritic cells (mDCs), but not in plasmacytoid dendritic cells (pDCs), suggesting that cellular susceptibility and cellintrinsic immune responses to ZIKV may differ among individual immune cell subsets[16]
To gain systemic insight into the immune response caused by ZIKV infection in humans, we conducted RNA sequencing (RNA-Seq)-based transcriptional profiling experiments to characterize gene expression changes in seven immune cell populations (CD4 T cells, CD8 T cells, B cells, natural killer (NK) cells, monocytes, mDCs, and pDCs) from the peripheral blood of three study individuals with acute ZIKV infection; cells from three gender- and age-matched healthy individuals were treated identically and were used as reference samples
Summary
Zika virus (ZIKV) is a mosquito-borne pathogen with increasing public health significance. While gene expression patterns from most cell subsets display signs of impaired antiviral immune activity, pDCs from infected host have distinct transcriptional response associated with activation of innate immune recognition and type I interferon signaling pathways, but downregulation of key host factors known to support ZIKV replication steps; pDCs exhibit a unique expression pattern of gene modules that are correlated with alternative cell populations, suggesting collaborative interactions between pDCs and other immune cells, B cells. The choice of dendritic cells (DCs) and monocytes as preferred target cells for ZIKV seems paradoxical, as these cells harbor a complex network of innate immune sensors that can recognize viral nucleic acids and activate potent type I interferon (IFN-I)-dependent cellintrinsic antiviral immune defense programs.
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