Abstract
AbstractSevere dengue (SD) is a major cause of morbidity and mortality impacting approximately 5 million of the 400 million people infected with dengue virus (DENV) annually. To define DENV target cells and immunological hallmarks of SD progression in children’s blood, we integrated virus-inclusive single cell RNA-Seq 2 (viscRNA-Seq 2) with functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion, and cell-cell communications point towards increased migration and inflammation in SD progressors (SDp). Concurrently, antigen presenting cells from SDp demonstrate intact uptake, yet impaired interferon responses and antigen presentation, in part DENV-modulated. Increased activation, regulation, and exhaustion of effector responses and expansion of HLA-DR-expressing, possibly compensatory, adaptive-like NK cells also characterize SDp. These findings reveal DENV target cells in the human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.
Publisher
Cold Spring Harbor Laboratory
Reference52 articles.
1. The global distribution and burden of dengue
2. A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever - single centre experience;JPMA. The Journal of the Pakistan Medical Association,2013
3. WHO Guidelines Approved by the Guidelines Review Committee. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. World Health Organization Copyright © 2009, World Health Organization.: Geneva, 2009.
4. Recent Shift in Age Pattern of Dengue Hemorrhagic Fever, Brazil
5. DIFFERENCES IN DENGUE SEVERITY IN INFANTS, CHILDREN, AND ADULTS IN A 3-YEAR HOSPITAL-BASED STUDY IN NICARAGUA
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献