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

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. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE103482 | GEO | 2018/03/14

REPOSITORIES: GEO

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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

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

Proteomic approach for the analysis response of macrophages to Borrelia burgdorferi

2018-10-22 | PXD008228 | Pride

CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia

Project description:Targeting the reprogramming and phagocytic capacities of tumor-associated macrophages (TAMs) has emerged as a therapeutic opportunity for cancer treatment. Here, we demonstrate that leukemic cell phagocytosis triggers the proinflammatory activation of TAMs as demonstrated by the upregulation and dowregulation of, respectively, proinflammatory and anti-inflammatory genes in phagocytic macrophages (Phago+) with respect to non-phagocytic macrophages (Phago-).

2022-10-25 | E-MTAB-12280 | biostudies-arrayexpress

Macrophage development and activation involve coordinated intron retention in key inflammatory regulators

Project description:Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using mRNA sequencing, bioinformatics analyses and RT-qPCR validation, we identified differential IR and altered expression of key genes involved in macrophage development and function, both in vitro and in vivo. We demonstrate that decreased IR in nuclear-detained mRNA is coupled to increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts in macrophages are rapidly spliced, leading to timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular mechanisms controlling vital regulators of the innate immune response.

2020-05-27 | PXD017391 | Pride

In vitro differentiation of M1, M2, and TAM-like macrophages from healthy donor PBMC

Project description:To understand the immunological role of different macrophage populations in the tumor, we generated transcriptional profiles of macrophages differentiated from PBMC-derived monocytes in vitro under three conditions to compare with: M1-like macrophages were developed in vitro through polarization of human monocytes by IFNg and TLR4 stimulation. This population is considered to have anti-tumor activities; releasing proinflammatory cytokines, performing phagocytosis, and possessing antigen cross presentation abilities. Second, M2-like macrophages were developed in vitro through intensive IL4 stimulation of monocytes. M2 macrophages are known to promote many pro-tumorigenic processes such as angiogenesis, immune suppression, hypoxia induction, tumor cell proliferation, metastasis. Lastly, we deployed a third population that represents a better in vitro model for tumor associated macrophages (TAM), developed under conditions better resembling the TME.Monoctyes derived from two individual patient donors were cultured separately under four (4) different conditions in vitro, for a total of eight (8) samples to be processed for bulk RNA sequencing.

2023-09-18 | GSE243175 | GEO

Transcription profiling time series of leaf epidermis from Hordeum vulgare Ingrid infected with Magnaporthe isolate TH6772 and Magnaporthe isolate CD180

Project description:Time course: Interaction of Magnaporthe isolate TH6772 (of the host plant rice) with Hordeum vulgare, Ingrid (leaf epidermis) and Magnaporthe isolate CD180 (of Pennisetum) with Hordeum vulgare, Ingrid (leaf epidermis)

2009-06-10 | E-IPKG-9 | biostudies-arrayexpress

RNA-seq gene expression profiling in resting murine B cells from WT or KMT2D knockout mice, before and after stimulation with LPS, IL4, and anti-CD180

Project description:Resting B cells were isolated from WT or KMTD KO mice by immunomagentic depletion of with anti-CD43 beads. Gene expression use determined by RNAseq in resting B cells or B cells stimulated with LPS, IL4, and anti-mouse CD180 for 3 days.

2017-08-28 | GSE68818 | GEO

Red blood cells from mice on high fat diet induce macrophage activation during phagocytosis

Project description:We studied macrophage gene expression from mice fed chow diet (C) or 60% high fat diet (HF), that phagocytized C-RBC, HFD-RBC, or no RBC. Macrophages from mice on HF diet were activated toward a pro-inflammatory phenotype. In macrophages isolated from CD mice, RBC phagocytosis yielded a gene expression pattern similar to HF macrophages. Incubation of HF-RBC with macrophages resulted in a significantly more pronounced upregulation of pro-inflammatory chemokines as compared to C-RBC. Peritoneal macrophages were obtained from C57BL/6 mice fed either C or HF diet. Phagocytosis was performed in vitro with C-RBC or HF-RBC; macrophages not exposed to RBC served as a control. Affymetrix Mouse Gene 1.0 ST microarray chips were used to assess the gene expression profile.

2013-08-28 | E-GEOD-50240 | biostudies-arrayexpress

Vitamin D regulates MerTK-dependent phagocytosis in human myeloid cells

Project description:Vitamin D deficiency is a major environmental risk factor for the development of multiple sclerosis (MS). The major circulating metabolite of vitamin D (25OHD) is converted to the active form (calcitriol) by the hydroxylase enzyme CYP27B1. In MS lesions the tyrosine kinase MerTK expressed by microglia and macrophages regulates phagocytosis of myelin debris and apoptotic cells that can accumulate and inhibit tissue repair and remyelination. We show that calcitriol downregulates MerTK mRNA and protein expression in primary adult human microglia and monocyte-derived macrophages, thereby inhibiting myelin phagocytosis and apoptotic cell clearance. Proinflammatory myeloid cells express high levels of CYP27B1 compared to homeostatic (TGFb-treated) myeloid cells. Only proinflammatory cells in the presence of TNF-a generate calcitriol from 25OHD, resulting in repression of MerTK expression and function. The selective production of calcitriol in proinflammatory myeloid cells leading to downregulation of MerTK-mediated phagocytosis has the potential to reduce the risk for auto-antigen presentation while retaining the phagocytic ability of homeostatic myeloid cells, thereby contributing to inflammation reduction and enhanced tissue repair.

2020-04-21 | GSE148986 | GEO

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