Adaptor protein-3 in dendritic cells facilitates phagosomal toll-like receptor signaling and antigen presentation to CD4(+) T cells.

Mantegazza AR, Guttentag SH, El-Benna J, Sasai M, Iwasaki A, Shen H, Laufer TM, Marks MS
Immunity. 2012 36 (5): 782-94

PMID: 22560444 · PMCID: PMC3361531 · DOI:10.1016/j.immuni.2012.02.018

Effective major histocompatibility complex-II (MHC-II) antigen presentation from phagocytosed particles requires phagosome-intrinsic Toll-like receptor (TLR) signaling, but the molecular mechanisms underlying TLR delivery to phagosomes and how signaling regulates antigen presentation are incompletely understood. We show a requirement in dendritic cells (DCs) for adaptor protein-3 (AP-3) in efficient TLR recruitment to phagosomes and MHC-II presentation of antigens internalized by phagocytosis but not receptor-mediated endocytosis. DCs from AP-3-deficient pearl mice elicited impaired CD4(+) T cell activation and Th1 effector cell function to particulate antigen in vitro and to recombinant Listeria monocytogenes infection in vivo. Whereas phagolysosome maturation and peptide:MHC-II complex assembly proceeded normally in pearl DCs, peptide:MHC-II export to the cell surface was impeded. This correlated with reduced TLR4 recruitment and proinflammatory signaling from phagosomes by particulate TLR ligands. We propose that AP-3-dependent TLR delivery from endosomes to phagosomes and subsequent signaling mobilize peptide:MHC-II export from intracellular stores.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (25)

Adaptor Protein Complex 3 Animals Antigen Presentation Antigens CD4-Positive T-Lymphocytes Cell Differentiation Cell Membrane Cells, Cultured Dendritic Cells Endocytosis Histocompatibility Antigens Class II Ligands Listeria monocytogenes Listeriosis Mice Mice, Inbred C57BL Mice, Transgenic Myeloid Differentiation Factor 88 Ovalbumin Peptides Phagocytosis Phagosomes Signal Transduction Th1 Cells Toll-Like Receptors

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