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

Seydoux, Emilie; Rothen-Rutishauser, Barbara; Nita, Izabela Magdalena; Balog, S; Gazdhar, Amiq Ur Rahman; Stumbles, PA; Petri-Fink, Alke; Blank, Fabian; Von Garnier, Christophe (2014). Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation. International journal of nanomedicine, 9, pp. 3885-3902. DOVE Medical Press 10.2147/IJN.S64353

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

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Seydoux, Emilie; Rothen-Rutishauser, Barbara; Nita, Izabela Magdalena; Gazdhar, Amiq Ur Rahman; Blank, Fabian and Von Garnier, Christophe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1176-9114

Publisher:

DOVE Medical Press

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

10 Mar 2015 12:47

Last Modified:

10 Mar 2015 12:47

Publisher DOI:

10.2147/IJN.S64353

PubMed ID:

25152619

Uncontrolled Keywords:

CD4+ T-cells, immune modulation, mouse dendritic cells, nanoparticles, polystyrene particles

BORIS DOI:

10.7892/boris.64352

URI:

https://boris.unibe.ch/id/eprint/64352

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