Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

• DOI: 10.2147/ijn.s64353
• Publication Date: 2014-08-14T01:29:31Z
• Authors: Emilie Seydoux; Barbara Rothen-Ru...; Izabela Nita; Amiq Gazdhar; Alke Petri-Fink; Fabian Blank; Christope von Gar...; Sandor Balog; Philip Stumbles
• Keywords: CD86; CD11c

Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, effects nanoparticles on DC function and downstream remain poorly understood.Bone marrow-derived DCs (BMDCs) were exposed vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, surface marker expression, soluble protein antigen degradation, well CD4(+) T-cell proliferation cytokine production analyzed flow cytometry. In addition, co-localization within lysosomal compartment, permeability, endoplasmic reticulum stress analyzed.The frequency PS particle-positive CD11c(+)/CD11b(+) BMDCs reached an early plateau after minutes was significantly higher for than at all time-points analyzed. did not alter viability modify expression markers CD11b, CD11c, MHC class II, CD40, CD86. Although particle exposure modulate uptake, decreased capacity degrade antigen, without affecting their ability induce antigen-specific proliferation. Co-localization studies between lysosomes using laser scanning confocal microscopy detected a co-localized compared with counterparts. Neither size caused leakage, gene markers, changes cytokines profiles.These data indicate that although supposedly inert activation alteration stimulating capacity, (but nm) reduce degradation through interference compartment. These findings emphasize importance performing in-depth analysis when developing novel approaches nanoparticles.