Nanoparticles target distinct dendritic cell populations according to their size.

The efficiency of a vaccine largely depends on the appropriate targeting of the innate immune system, mainly through prolonged delivery of antigens and immunomodulatory substances to professional antigen-presenting cells in the lymphoid environment. Particulate antigens, such as virus-like particles...

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المؤلفون الرئيسيون: Manolova, V, Flace, A, Bauer, M, Schwarz, K, Saudan, P, Bachmann, M
التنسيق: Journal article
اللغة:English
منشور في: 2008
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author Manolova, V
Flace, A
Bauer, M
Schwarz, K
Saudan, P
Bachmann, M
author_facet Manolova, V
Flace, A
Bauer, M
Schwarz, K
Saudan, P
Bachmann, M
author_sort Manolova, V
collection OXFORD
description The efficiency of a vaccine largely depends on the appropriate targeting of the innate immune system, mainly through prolonged delivery of antigens and immunomodulatory substances to professional antigen-presenting cells in the lymphoid environment. Particulate antigens, such as virus-like particles (VLP) induce potent immune responses. However, little is known about the relative importance of direct drainage of free antigen to lymph nodes (LN) versus cellular transport and the impact of particle size on the process. Here, we show that nanoparticles traffic to the draining LN in a size-dependent manner. Whereas large particles (500-2000 nm) were mostly associated with dendritic cells (DC) from the injection site, small (20-200 nm) nanoparticles and VLP (30 nm) were also found in LN-resident DC and macrophages, suggesting free drainage of these particles to the LN. In vivo imaging studies in mice conditionally depleted of DC confirmed the capacity of small but not large particles to drain freely to the LN and demonstrated that DC are strictly required for transport of large particles from the injection site to the LN. These data provide evidence that particle size determines the mechanism of trafficking to the LN and show that only small nanoparticles can specifically target LN-resident cells.
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spelling oxford-uuid:9a6a4ffc-b4f6-4517-ad0c-faba6091f6fc2022-03-27T00:21:10ZNanoparticles target distinct dendritic cell populations according to their size.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9a6a4ffc-b4f6-4517-ad0c-faba6091f6fcEnglishSymplectic Elements at Oxford2008Manolova, VFlace, ABauer, MSchwarz, KSaudan, PBachmann, MThe efficiency of a vaccine largely depends on the appropriate targeting of the innate immune system, mainly through prolonged delivery of antigens and immunomodulatory substances to professional antigen-presenting cells in the lymphoid environment. Particulate antigens, such as virus-like particles (VLP) induce potent immune responses. However, little is known about the relative importance of direct drainage of free antigen to lymph nodes (LN) versus cellular transport and the impact of particle size on the process. Here, we show that nanoparticles traffic to the draining LN in a size-dependent manner. Whereas large particles (500-2000 nm) were mostly associated with dendritic cells (DC) from the injection site, small (20-200 nm) nanoparticles and VLP (30 nm) were also found in LN-resident DC and macrophages, suggesting free drainage of these particles to the LN. In vivo imaging studies in mice conditionally depleted of DC confirmed the capacity of small but not large particles to drain freely to the LN and demonstrated that DC are strictly required for transport of large particles from the injection site to the LN. These data provide evidence that particle size determines the mechanism of trafficking to the LN and show that only small nanoparticles can specifically target LN-resident cells.
spellingShingle Manolova, V
Flace, A
Bauer, M
Schwarz, K
Saudan, P
Bachmann, M
Nanoparticles target distinct dendritic cell populations according to their size.
title Nanoparticles target distinct dendritic cell populations according to their size.
title_full Nanoparticles target distinct dendritic cell populations according to their size.
title_fullStr Nanoparticles target distinct dendritic cell populations according to their size.
title_full_unstemmed Nanoparticles target distinct dendritic cell populations according to their size.
title_short Nanoparticles target distinct dendritic cell populations according to their size.
title_sort nanoparticles target distinct dendritic cell populations according to their size
work_keys_str_mv AT manolovav nanoparticlestargetdistinctdendriticcellpopulationsaccordingtotheirsize
AT flacea nanoparticlestargetdistinctdendriticcellpopulationsaccordingtotheirsize
AT bauerm nanoparticlestargetdistinctdendriticcellpopulationsaccordingtotheirsize
AT schwarzk nanoparticlestargetdistinctdendriticcellpopulationsaccordingtotheirsize
AT saudanp nanoparticlestargetdistinctdendriticcellpopulationsaccordingtotheirsize
AT bachmannm nanoparticlestargetdistinctdendriticcellpopulationsaccordingtotheirsize