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Proteomic approach for the analysis response of macrophages to Borrelia burgdorferi

ABSTRACT: Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. In this work we tried to uncover the biosignature of murine bone marrow-derived macrophages and human blood monocytes upon Borrelia infection using transcriptomics and proteomics approaches.

OTHER RELATED OMICS DATASETS IN: GSE103483PRJNA401784PRJNA401425PRJNA401732

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Borrelia Sp. Bc7 Mus Musculus (mouse)

TISSUE(S): Macrophage

DISEASE(S): Lyme Disease

SUBMITTER: Mikel Azkargorta

LAB HEAD: Felix Elortza

PROVIDER: PXD008228 | Pride | 2018-10-22

REPOSITORIES: Pride

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A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.

Carreras-González Ana A Navasa Nicolás N Martín-Ruiz Itziar I Lavín José Luis JL Azkargorta Mikel M Atondo Estíbaliz E Barriales Diego D Macías-Cámara Nuria N Pascual-Itoiz Miguel Angel MA Sampedro Leticia L Tomás-Cortázar Julen J Peña-Cearra Ainize A Pellón Aize A Prados-Rosales Rafael R Abecia Leticia L Elortza Félix F Aransay Ana M AM Rodríguez Héctor H Anguita Juan J

Emerging microbes & infections 20180307 1

Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signaling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomic and proteomic approaches. We identified a common pattern of genes that are transcriptionally regulated and overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens ...[more]

PMID: 29511161

Similar Datasets

Macrophage responses to persistent Borrelia burgdorferi stimulation modulates host inflammation and results in tissue-wide transcriptional and proteomic changes during Lyme carditis

Project description:Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and other less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound downregulation of mitochondrial components. We also characterize the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced IRF-4-dependent inflammatory responses. In vitro, glycolysis inhibition reduces the production of TNF by memory macrophages whereas in vivo, it produces the reversion of the Irf4-induced memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.

2021-09-09 | PXD019605 | Pride

A multi-omic analysis reveals a regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi [microarray]

Project description:Macrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response.

2018-03-14 | GSE103481 | GEO

A multi-omic analysis reveals a regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi [RNA-Seq]

2018-03-14 | GSE103482 | GEO

Regulation of Borrelia burgdorferi-induced macrophage activity by spirochetal-regulated surface receptors

Project description:Macrophages mediate the elimination of pathogens by phagocytosis resulting in the activation of specific signaling pathways that lead to the production of cytokines, chemokines and other factors. Borrelia burgdorferi, the causative agent of Lyme disease, causes a wide variety of pro-inflammatory symptoms. The proinflammatory capacity of macrophages is intimately related to the internalization of the spirochete. However, most receptors mediating this process are largely unknown. We have applyedapplied a multiomic approach, including the proteomic analysis of B. burgdorferi-containing phagosome-enriched fractions, to identify surface receptors that are involved in the phagocytic capacity of macrophages as well as their inflammatory output. Sucrose gradient protein fractions of human monocyte-derived macrophages exposed to B. burgdorferi contained the phagocytic receptor, CR3/CD14 highlighting the major role played by these proteins in spirochetal phagocytosis. Among others, Other proteins identified proteins include C-type lectins, scavenger receptors or siglecs, and contain uPAR and MARCO. We also identified the Fc gamma receptor pathway as involved both in the phagocytosis of , and TNF induction by B. burgdorferi in the absence of antibodies. The common gamma chain, FcR, mediates the phagocytosis of the spirochete, likely through Fc receptors and C-type lectins, in a process that involves Syk activation. Overall, these findings highlight the complex array of receptors involved in the phagocytic response of macrophages to B. burgdorferi.

2019-12-06 | PXD012854 | Pride

The Lipid Raft Proteome of Borrelia burgdorferi.

Project description:Eukaryotic lipid rafts are membrane microdomains rich in cholesterol that contain a selective set of proteins, and have been associated with multiple biological functions. The Lyme disease agent, Borrelia burgdorferi, is one of an increasing number of bacterial pathogens that incorporates cholesterol onto its membrane, and form cholesterol glycolipid domains that possess all the hallmarks of eukaryotic lipid rafts. In this study, we isolated lipid rafts from cultured B. burgdorferi as a detergent resistant membrane (DRM) fraction on density gradients, and characterized those molecules that partitioned exclusively or are highly enriched in these domains. Cholesterol glycolipids, the previously known raft-associated lipoproteins OspA and OpsB, and cholera toxin partitioned into the lipid rafts fraction indicating compatibility with components of the DRM. The proteome of lipid rafts was analyzed by a combination of LC-MS/MS or MudPIT. Identified proteins were analyzed in silico for parameters that included localization, isoelectric point, molecular mass and biological function. The proteome provided a consistent pattern of lipoproteins, proteases and their substrates, sensing molecules, and prokaryotic homologs of eukaryotic lipid rafts. This study provides the first analysis of a prokaryotic lipid raft and has relevance for the biology of Borrelia, other pathogenic bacteria, as well as for the evolution of these structures.

2015-09-21 | PXD002365 | Pride

Macrophage training to Borrelia burgdorferi governs cardiac inflammation in the mammalian host [RNA-seq]

Project description:Macrophage exposure to vaccine or vaccine-like formulations results in disparate secondary responses. We have identified the transcriptomic and metabolic changes associated with the memory response of macrophages to Borrelia burgdorferi, an extracellular pathogen able to establish long-term infections in mammals. Memory macrophages show an enhanced ability to bind and internalize the spirochete with decreased inflammatory responses, in part regulated by Irf4. Experienced macrophages also show an augmented glycolytic output. In vivo, glycolysis inhibition results in decreased cardiac inflammation and reduced expression of Irf4. Our data show that B. burgdorferi induces long-term, memory-like responses that are amenable to be manipulated in vivo.

2021-01-21 | GSE125503 | GEO

Acetylation in Borrelia burgdorferi

Project description:Borelia burgdorferi, the causative agent of the Lyme disease, cycles between a vector (tick) and the mammalian host. Our principal goal is to study how B. burgdorferi adapts its metabolism to colonize and survive in the tick. We established the first growth-phase related acetylome and demonstrated the role of acetylation on central metabolism regulation. We also demonstrated that acetyl phosphate is the primary acetyl donor in B. burgdorferi.

2018-09-24 | PXD010065 | Pride

A quantitative model for macrophage activation predicts tunable distance thresholds for propagation of inflammationes in response LPS stimulation

Project description:Label free analysis of the secretome of RAW264.7 murine macrophages in response to LPS stimulation.

2015-11-30 | PXD001905 | Pride