Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.
Luca GhitaZhiyuan YaoYike XieVeronica DuranHalise Busra CagiriciJerome SamirIlham OsmanDavid Esteban Rebellón-SánchezOlga Lucia Agudelo-RojasAna Maria SanzMalaya Kumar SahooMakeda L RobinsonRosa Margarita Gelvez-RamirezNathalia BuenoFabio LucianiBenjamin A PinskyJose G MontoyaMaria Isabel Estupiñan-CardenasLuis Angel Villar-CentenoElsa Marina Rojas-GarridoFernando RossoStephen R QuakeFabio ZaniniShirit EinavPublished in: Nature immunology (2023)
Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and 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 as well as cell-cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.
Keyphrases
- dengue virus
- single cell
- induced apoptosis
- zika virus
- rna seq
- cell cycle arrest
- high throughput
- aedes aegypti
- genome wide
- cell migration
- oxidative stress
- dendritic cells
- gene expression
- signaling pathway
- acute myeloid leukemia
- drug delivery
- cell death
- bone marrow
- sars cov
- regulatory t cells
- stem cells
- transcription factor
- cell therapy
- cancer therapy
- drug induced