Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Borrelia burgdorferi induces durable tolerogenic reprogramming in bone marrow cells

ABSTRACT: Borrelia burgdorferi (Bb), the causative agent of Lyme disease, is known for its remarkable ability to persist within mammalian hosts. The dynamic host-pathogen interaction induces acute inflammation as well as lasting changes in host immunity. Here, we show that Bb infection leads to persistent transcriptional reprogramming in the bone marrow, the site of hematopoiesis. This unique response is characterized by early induction of interferon-stimulated genes accompanied by sustained suppression of other classical proinflammatory pathways throughout infection. Functionally, bone marrow-derived macrophages (BMDMs) from Bb infected mice exhibit a significant reduction in proinflammatory cytokine production upon secondary ex vivo Bb stimulation, suggesting a tolerogenic imprinting of the myeloid lineage. We show that this tolerogenic state is rooted in a remodeled chromatin landscape of those macrophages, characterized by reduced accessibility of proinflammatory transcription factor motifs. Interestingly, this dampened pro-inflammatory response persists for at least 15 weeks post Bb infection and is partially maintained even after pathogen clearance by antibiotic treatment, despite restoration of certain proinflammatory transcripts in the bone marrow. Our findings reveal a prolonged form of innate immune tolerance imprinted by Bb infection, with potential implications for post-infectious immune function in Lyme disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE314798 | GEO | 2026/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Borrelia burgdorferi infected Ixodes scapularis nymph saliva proteome

Project description:Lyme disease (LD) is one of the most important human vector-borne diseases in North America. Since transmission of Borrelia burgdorferi (Bb), the causative agent of LD, is influenced by yet unknown tick saliva proteins (TSP), the discovery and characterization of such TSPs are highly sought after for their potential as tick-antigen based vaccine targets. We validated a novel non-invasive approach of collecting sufficient amounts of saliva from unfed, partially fed (12, 24, 36, 48, 60, and 72h), and replete fed Ixodes scapularis nymphs for identification of tick saliva proteins using the LC-MS/MS approach. Our data has described TSPs that might be injected into the host within few hours of the tick starting to feed and are likely associated with manipulating host immunity to facilitate transmitted Bb to colonize the host. Thus, these data will serve as a source for Bb-infection associated TSPs that might be targeted in tick-antigen based vaccines to prevent LD. Equally important, the non-invasive method to collect nymph tick saliva is likely to provide transformative impact on research to understand transmission of other TBD agents.

2021-09-10 | PXD023940 | Pride

Spatial Transcriptomic Profiling Reveals Joint Inflammation Signatures in Borrelia burgdorferi–Infected C3H Mice

Project description:Lyme arthritis, a manifestation of Lyme disease, is triggered by the spirochetal bacterium Borrelia burgdorferi (Bb), which is transmitted through the bite of the Ixodes tick. Although multiple studies have been performed on the complex host immune response in Lyme arthritis, the spatial gene expression environment in the joint tissue remains unexplored. Here, we applied spatial transcriptomics to ankle joints of C3H mice infected with B. burgdorferi, profiling tissues at peak inflammation (2 weeks post infection) and after antibiotics (4 weeks post-infection) during inflammation resolution. Analysis revealed spatially restricted signatures: pro-inflammatory responses dominated synovial and fibroblast populations 2 weeks post-infection, with elevated levels of Vimentin and I-Ek related gene and protein expression localized to these regions. In contrast, 4 weeks post-infection during the inflammation resolution phase, levels of Vimentin and I-Ek related gene and protein expression are reduced drastically despite the persistent pathology seen by H&E staining. Notably, fibroblasts and synoviocytes in the medial humeroulnar joint regions adopted immune-like phenotypes during peak inflammation, while the same cell types in the lateral humeroradial joint displayed a more infection-resilient phenotype. Comparison with scRNA-seq synoviocyte cluster revealed little overlap, but concordant genes that were upregulated were involved in ECM remodeling (Col1a1, Col3a1, Mmp2, Timp1), fibroblast activation (Postn, Runx1, Ctnnb1), and inflammation (Saa3, Ccl7, Tnfaip6). By week 4, concordant downregulation of genes coding for ribosomal proteins, mitochondrial complex subunits, and Jun (an immediate-early inflammatory gene) was noted. These spatially resolved maps demonstrate that joint microenvironments play a crucial role in pathogenesis, offering unique insights into Lyme arthritis pathology.

2026-07-23 | GSE327700 | GEO

RNAseqcharacterization ofB. burgdorferi-inducedinnate immune memoryandregulation ofLyme carditis through Acod1

Project description:Borrelia burgdorferi (Bb), which causes Lyme disease, establishes long term infection and leads to disease manifestations that are mostly a result of host immune responses to the pathogen. Disease symptoms often resolve without treatment, suggesting innate immune memory may play a role in dampening inflammation over time. We used an in vitro model of repeated stimulations in macrophage and performed RNA sequencing on acute and memory states. We categorized differentially expressed genes based on their response to acute infection as well as their memory response compared to acute. We discuss four expression subsets representing important cellular changes to repeated stimulation and focus on genes that are negative regulators of inflammation induced during the acute phase and mediate long-term immunosuppression. We identified Aconitate decarboxylase 1 (Acod1), a negative regulator of inflammatory responses, and confirmed its role during in vivo long-term infection with Bb, with a specific role in Lyme carditis.

2023-11-01 | GSE236149 | GEO

Borrelia burgdorferi induces durable tolerogenic reprogramming in bone marrow cells

Project description:Borrelia burgdorferi induces durable tolerogenic reprogramming in bone marrow cells

| PRJNA1392615 | ENA

Evaluation of Peromyscus leucopus Bone Marrow-Derived Macrophage Responses to Borrelia burgdorferi and Lipopolysaccharide

Project description:Currently, most tools utilized in host-pathogen interaction studies depend on the use of human or mouse (Mus musculus) cells and tissues. While these species have led to countless breakthroughs in our understanding of infectious disease, there are undoubtably important biological processes that are missed by limiting studies to these two vertebrate species. For instance, it is well-established that the most common North American rodent, the Peromyscus leucopus deermouse, has unique interactions with microbes, which likely shape its ability to serve as a critical reservoir for at numerous zoonotic pathogens—including a Lyme disease spirochete, Borrelia burgdorferi. In this work, we expand the immunological toolkit to study P. leucopus biology by performing the first differentiation of deermouse bone marrow to macrophages using P. leucopus M-CSF producing HEK293T cells.

2025-05-08 | GSE283617 | GEO

Uptake of exogenous phospholipids by Borrelia burgdorferi

Project description:The Lyme disease pathogen Borrelia burgdorferi can take up environmental phospholipids for membrane biosynthesis. These phospholipids include those also produced de novo by the bacterium (PC and PG) and some that are mammalian-like. We examined the effect of exogenous phospholipids on gene expression.

2025-12-19 | GSE304281 | GEO

Lizard feeding enhances Ixodes pacificus vector competence

Project description:Ixodes pacificus, the vector of Borrelia burgdorferi (Bb) on the west coast, feeds on a variety of hosts including rodents, birds, and lizards. While rodents are reservoirs for Bb and can infect juvenile ticks, lizards are Bb-refractory. Despite the range of bloodmeals for I. pacificus, it is undetermined how larval host bloodmeal identity may affect future nymphal vector competence. Here, we conducted a transcriptome analysis on I. pacificus to determine whether and through what mechanisms host bloodmeal history affects vector competency of I. pacificus for the Lyme disease pathogen.

2021-04-27 | GSE173109 | GEO

Single-cell RNA seq identifies genes regulating the inflammatory pathways activated by purified Borrelia burgdorferi lipoproteins in murine bone marrow derived macrophages

Project description:Borrelia burgdorferi, the spirochetal agent of Lyme disease, has a large constellation of lipoproteins that play a prominent role in mediating pathogen-specific interactions with tick and vertebrate host cells. Although there is a large body of information on the effects of borrelial lipoproteins on immune modulatory pathways, the application of multi-omics methodologies to decode the transcriptional and proteomic patterns associated with host cell responses induced by lipoproteins in murine bone-marrow macrophages (BMDM) have helped identify additional effectors/pathways. Single-cell RNA seq revealed spatial heterogeneity within BMDM. Gene expression analysis showed that genes involved in pathways such as MAPK, TLR, NOD, chemokines, T-cell receptor signaling are activated in BMDM with unbiased proteomics analysis corroborating these findings.

2025-01-29 | GSE253285 | GEO

Single Cell Immunophenotyping of Lyme Erythema Migrans (Bulk TCR Repertoire Sequencing)

Project description:Erythema migrans (EM) is a skin lesion caused by the spirochete B. burgdorferi (Bb) and is a hallmark initial sign of Lyme disease. Previous studies have demonstrated that T cells and innate immune cells mediate local inflammatory cytokine production that promote the reaction. Despite the established importance of B cells and antibodies in preventing Bb infection and resolving disease, the role of B cells in the skin immune response to Bb is incompletely defined. In this study, we characterized the immunophenotype of EM lesions and used single cell RNA-Seq to investigate B cell receptor (BCR) and T cell receptor (TCR) repertoires in the EM skin lesions and peripheral blood of patients with Lyme disease. We hypothesized that B cells from the circulation, potentially primed by exposure to Bb antigens in regional draining lymph nodes, are recruited into EM lesions and play an active role in the local response to infection. We found that B cells are more abundant in the EM lesion in comparison to autologous uninvolved skin and possess distinct characteristics, including abundant expression of MHCII genes and preferential IgM isotype usage. A subset exhibited low levels of somatic hypermutation despite a gene expression profile more consistent with memory than naïve B cell subsets. Moreover, infiltrating B cells were clonally expanded and a large fraction could be directly traced to circulating relatives. By leveraging single cell gene expression with paired BCR and TCR repertoire sequencing, we demonstrate, for the first time, that B cells are recruited to the skin infection site in early Lyme disease and express a phenotype suggesting that they could play a role in local antigen presentation and antibody production.

2021-06-07 | GSE172225 | GEO

Single Cell Immunophenotyping of Lyme Erythema Migrans (Bulk BCR Repertoire Sequencing)

2021-06-07 | GSE171215 | GEO