iPS cell serves as a source of dendritic cells for in vitro dengue virus infection model

Area of Science:

• Immunology
• Virology
• Stem Cell Biology

Background:

• Developing effective dengue virus (DENV) models for immune response and vaccine research is crucial but hindered by limitations of traditional dendritic cells (DC).
• Monocyte-derived dendritic cells (moDC) have been used, but face challenges with quantity, proliferation, and donor variability.
• Human induced pluripotent stem cells (iPSC) offer consistent proliferation, stable characteristics, and customizable HLA backgrounds, presenting a promising alternative.

Purpose of the Study:

• To evaluate the potential of iPSC-derived dendritic cells (iPSC-ML-DC) as a reliable in vitro model for DENV studies.
• To compare the characteristics and functionality of iPSC-ML-DC with traditional moDC in the context of DENV infection and T cell activation.

Main Methods:

• Utilized iPSC (HLA-A*24) as a source for dendritic cell generation (iPSC-ML-DC).
• Assessed DENV infectivity, major surface marker expression, and cytokine production potential of iPSC-ML-DC.
• Evaluated the ability of DENV-infected iPSC-ML-DC to activate HLA-matched and mismatched T cells in vitro.

Main Results:

• iPSC-ML-DC exhibited comparable DC marker expression, DENV infection efficiency, and cytokine production to moDC.
• DENV-infected iPSC-ML-DC successfully activated HLA-matched T cells, indicated by increased IFN-γ+ CD69+ T cells.
• No significant T cell activation was observed with HLA-mismatched T cells, confirming antigen-specific activation.

Conclusions:

• iPSC-ML-DC demonstrate maturation potential, efficient DENV infection, and effective antigen-specific T cell activation capabilities.
• These findings suggest iPSC-ML-DC are a viable and attractive alternative to traditional DCs for in vitro DENV research.
• The developed iPSC-ML-DC model holds promise for advancing dengue immune response and vaccine development studies.