The Interaction of Borrelia burgdorferi with Human Dendritic Cells: Functional Implications.

Autor:	Gutierrez-Hoffmann M; Lyme Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD., Fan J; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD., O'Meally RN; Mass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD., Cole RN; Mass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD., Florea L; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD., Antonescu C; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD., Talbot CC; Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, MD., Tiniakou E; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD., Darrah E; Lyme Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD., Soloski MJ; Lyme Disease Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2023 Aug 15; Vol. 211 (4), pp. 612-625.
DOI:	10.4049/jimmunol.2300235
Abstrakt:	Dendritic cells bridge the innate and adaptive immune responses by serving as sensors of infection and as the primary APCs responsible for the initiation of the T cell response against invading pathogens. The naive T cell activation requires the following three key signals to be delivered from dendritic cells: engagement of the TCR by peptide Ags bound to MHC molecules (signal 1), engagement of costimulatory molecules on both cell types (signal 2), and expression of polarizing cytokines (signal 3). Initial interactions between Borrelia burgdorferi, the causative agent of Lyme disease, and dendritic cells remain largely unexplored. To address this gap in knowledge, we cultured live B. burgdorferi with monocyte-derived dendritic cells (mo-DCs) from healthy donors to examine the bacterial immunopeptidome associated with HLA-DR. In parallel, we examined changes in the expression of key costimulatory and regulatory molecules as well as profiled the cytokines released by dendritic cells when exposed to live spirochetes. RNA-sequencing studies on B. burgdorferi-pulsed dendritic cells show a unique gene expression signature associated with B. burgdorferi stimulation that differs from stimulation with lipoteichoic acid, a TLR2 agonist. These studies revealed that exposure of mo-DCs to live B. burgdorferi drives the expression of both pro- and anti-inflammatory cytokines as well as immunoregulatory molecules (e.g., PD-L1, IDO1, Tim3). Collectively, these studies indicate that the interaction of live B. burgdorferi with mo-DCs promotes a unique mature DC phenotype that likely impacts the nature of the adaptive T cell response generated in human Lyme disease. (Copyright © 2023 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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