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Toll-like receptor activation remodels the cell-surface proteome of human dendritic cells

ABSTRACT: Dendritic cells (DCs) are specialized sentinel and antigen presenting cells coordinating innate and adaptive immunity. Through proteins on their cell surface, DCs sense changes in the environment, internalize pathogens, present processed antigens, and communicate with other immune cells. By combining chemical labeling and quantitative mass spectrometry, we systematically profiled and compared the cell-surface proteomes of human primary conventional DCs (cDCs) in their resting and activated states. Toll-like receptor activation by a lipopeptide globally reshaped the cell-surface proteome of cDCs, with more than one hundred proteins up or down regulated. By simultaneously elevating positive regulators and reducing inhibitory signals across multiple protein families, the remodeling creates a cell-surface milieu promoting immune responses. Still, cDCs maintain the stimulatory-to-inhibitory balance by leveraging a distinct set of inhibitory molecules. This analysis thus uncovers the molecular complexity and plasticity of the cDC cell surface and provides a roadmap for understanding cDC activation and signaling.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000092573 | MassIVE | Wed Aug 02 09:04:00 BST 2023

REPOSITORIES: MassIVE

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