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Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay
Journal article   Open access   Peer reviewed

Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay

Peter Deak, Flora Kimani, Brittney Cassaidy and Aaron Esser-Kahn
Frontiers in immunology, v 11, 642
Apr 2020
PMID: 32328073
url
https://doi.org/10.3389/fimmu.2020.00642View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Animals Cell Adhesion Cells, Cultured Humans Immunity, Innate Immunoassay - methods Lipid A - analogs & derivatives Lipid A - chemistry Lipid A - metabolism Lymphocytes - metabolism Microplastics - chemistry Oligopeptides - chemistry Oligopeptides - metabolism Polystyrenes - chemistry Toll-Like Receptor 2 - agonists Toll-Like Receptor 2 - chemistry Toll-Like Receptor 2 - metabolism Toll-Like Receptor 4 - agonists Toll-Like Receptor 9 - agonists Toll-Like Receptor 9 - chemistry Toll-Like Receptor 9 - metabolism Toll-Like Receptors - agonists Tumor Necrosis Factor-alpha - metabolism
It is unknown if surface bound toll-like-receptor (TLR) agonists activate cells via density or total molecular number. To answer this question, we developed a TLR agonist surface conjugated polystyrene microparticle (MP) system. Using a library of MPs with varying TLR agonist density and number, we simultaneously observed innate immune cell MP uptake and TNFα expression using ImageStream flow cytometry on a cell by cell basis. The data shows that total TLR number and not density drives cellular activation with a threshold of approximately 10 -10 TLR agonists. We believe that this information will be crucial for the design of particulate vaccine formulations.

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Immunology
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