Activation of the inflammasome and enhanced migration of microparticle-stimulated dendritic cells to the draining...

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology

Background:

• Porous silicon microparticles (PSM) can be engineered to present pathogen-associated molecular patterns (PAMPs).
• This mimicry enhances cellular uptake and immune activation by antigen-presenting cells.

Purpose of the Study:

• To investigate the immunomodulatory effects of PAMP-bound PSM.
• To evaluate their potential in enhancing dendritic cell (DC) activation and T cell responses.

Main Methods:

• Murine bone marrow-derived dendritic cells (BMDCs) were incubated with PSM bound to Toll-like receptor 4 (TLR-4) ligands (LPS and MPL).
• Inflammasome activation (IL-1β production), DC maturation (costimulatory and MHC molecule expression), and migration were assessed.
• In vivo studies in mice involved inoculation with ligand-bound PSM and analysis of cytokine profiles and T cell activation using two-photon microscopy.

Main Results:

• PSM bound with LPS and MPL showed abundant uptake by BMDCs.
• Ligand-bound PSM induced concentration-dependent IL-1β production, indicating NLRP3 inflammasome activation.
• In vivo administration increased circulating IL-1β, TNF-α, and IL-6 levels.
• BMDC stimulation enhanced costimulatory molecule expression, MHC presentation, and migration to lymph nodes.
• PSM facilitated in vivo and in vitro immunological synapse formation between DCs and T cells, leading to enhanced T cell activation and interferon-gamma production.

Conclusions:

• Ligand-bound porous silicon microparticles are efficiently phagocytosed and activate the inflammasome in dendritic cells.
• These microparticles promote DC maturation, migration, and enhance antigen-specific T cell activation.
• Engineered PSM represent a promising platform for modulating immune responses.