Contrasting behavior between the three human monocyte subsets in dengue pathophysiology

Understanding antibody-dependent enhancement in dengue: Are afucosylated IgG1s a concern?

“…Lastly, immune cell populations and subpopulations are known to express different levels and types of FcγR, which can change during an infection. For example, FcγRIIa expression can be down-regulated in classical monocytes and up-regulated in intermediate and nonclassical monocytes in dengue [ 18 , 19 ]. Whether or not these changes influence the risk of ADE remains to be determined.…”

Global and cell type-specific immunological hallmarks of severe dengue progression

“…While patient-derived monocyte subtypes demonstrate comparable expression of DENV E protein levels and upregulation of genes and ligand-receptor interactions promoting inflammation and migration in SDp, their abundances are altered differently. Classical monocytes are expanded and activated, possibly contributing to SD pathogenesis by promoting migration to lymphoid organs, conferring sustained inflammation and forming a niche for DENV replication, as suggested by others 29 . Contrastingly, the fraction of non-classical monocytes—cells implicated in patrolling the endothelium and protecting from protease-mediated damage 29 —is drastically reduced, potentially impairing immune surveillance and contributing to the endothelial damage observed in SD 30 .…”

“…Classical monocytes are expanded and activated, possibly contributing to SD pathogenesis by promoting migration to lymphoid organs, conferring sustained inflammation and forming a niche for DENV replication, as suggested by others 29 . Contrastingly, the fraction of nonclassical monocytes-cells implicated in patrolling the endothelium and protecting from protease-mediated damage 29 -is drastically reduced, potentially impairing immune surveillance and contributing to the endothelial damage observed in SD 30 . APCs downregulate MHC-II genes involved in antigen presentation in SDp vs. D and reduce cell surface expression of HLA-DR protein in DENV-infected patients vs. healthy, as also observed via CyTOF 17 .…”

Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics

“…While CD16 + monocyte abundance in D was maintained at similar levels to controls, in SDp, despite increased Ki-67 expression, their abundance was lower than in D. This inadequate expansion of cells with antiviral functions suggests potential impairments in scavenging infected cells, neutrophil recruitment, and patrolling, leading to reduced viral clearance and antigen presentation in SDp ( 52 , 53 ). Notably, nonclassical monocytes demonstrated reduced abundance in SDp and distinct transcriptomic signatures in DENV-infected individuals in an Indian dengue cohort, highlighting the generalizability of these findings across diverse genetic backgrounds ( 54 ). The lower expression of HLA-DR on CD16 + (and DN monocytes and cDC2s) in SDp provides additional evidence for impaired antigen presentation by these myeloid cell subtypes.…”