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Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

ABSTRACT: Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

PROVIDER: PRJNA638542 | ENA |

REPOSITORIES: ENA

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Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

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.

2020-12-22 | GSE152168 | GEO

Borrelia burgdorferi induces a type I interferon response during early stages of disseminated infection in mice

Project description:Background: Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. Results: Borrelia burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P<0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included IFN-responsive genes and genes involved in immunity and inflammation. In contrast, B. burgdorferi B331, a clinical isolate that causes transient skin infection but does not disseminate in C3H/HeJ mice, stimulated changes in only a few genes (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by quantitative RT-PCR in mouse skin biopsies collected from the site of infection 24 hours after inoculation with B. burgdorferi. The mean values for transcript of Ifnb, Cxcl10, Gbp1, Ifit1, Ifit3, Irf7, Mx1, and Stat2, were found to be significantly increased in B. burgdorferi strain B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B. burgdorferi strain B331 or B31-4, a mutant that is unable to disseminate. Conclusions: These results establish a positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction in a murine model of Lyme disease.

2016-03-25 | E-MTAB-3325 | biostudies-arrayexpress

microRNA changes in astrocytes following Borrelia burgdorferi infection

Project description:miRNA profiles of astrocytes infected with Borrelia burgdorferi for 24 hours, 48 hours, and 24 hour uninfected controls were generated by deep sequencing, in duplicate, using Illumina MiSeq.

2017-02-01 | GSE85142 | GEO

Transcriptional profiling of the Borrelia burgdorferi bb0647 mutant

Project description:RNA was isolated from late-log pahse wild-type Borrelia burgdorferi B31 and the bb0647 mutant grown in BSKH media at 37 degree, 5% CO2. cDNA was synthesized, labeled and hybridized to the 70mer oligonucleotide B. burgdorferi array. Slides were scanned using axon scanner and image were analyzed using GenePix 6.0. Dta were further analysed using the professional software Acuity 4.o, based on a ratio-based normalization. Samples were labeled by either Cy3 or Cy5. 5 hybs were performed, including dye-swaps.

2010-05-15 | E-GEOD-17422 | biostudies-arrayexpress

Transcriptional profiling of the Borrelia burgdorferi bb0647 mutant

2010-01-20 | GSE17422 | GEO

SR0726 deletion leads to altered transcriptome of cultured Borrelia burgdorferi

Project description:Differential gene expression analysis was performed to assess the affects of the deletion of sRNA SR0726 on the in vitro transcriptome of Borrelia burgdorferi in order to investigate a potential regulatory role for the sRNA

2022-02-27 | GSE197340 | GEO

Identification of the differences between gene expression in normal human dermal fibroblasts (NHDF cell line) infected with Borrelia burgdorferi sensu lato spirochetes

Project description:The similarity of Lyme borreliosis to other diseases and the complex pathogenesis cause diagnostic and therapeutic difficulties. Changes at the cellular and molecular level after Borrelia sp. infection remain still poorly understood. Therefore, the present study focused on the gene expression in human dermal fibroblasts in differentiation of infection with Borrelia garinii, Borrelia afzelii and Borrelia burgdorferi sensu stricto spirochetes. For microarray analysis 10 samples were used: 3 control samples - K, 2 samples of NHDF cells infected with Borrelia garinii - G, 2 samples of NHDF cells infected with Borrelia afzelii - A and 3 samples of NHDF cells infected with Borrelia burgdorferi sensu stricto - SS.

2015-05-12 | E-GEOD-68741 | biostudies-arrayexpress

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.

Project description: Not available

| S-EPMC7808612 | biostudies-literature

Transcriptional responses of normal human dermal fibroblasts (NHDF) induced by Borrelia burgdorferi sensu stricto

Project description:The aim of the study was to compare the global transcriptional responses elicited in NHDF cells by three different strains of Borrelia burgdorferi ss (the agent of Lyme borreliosis), representative of different stages in the life cycle of Borrelia: one reference strain isolated from a tick (strain N40), and two invasive strains isolated from skin biopsy of erythema migrans (strain Pbre c4) and acrodermatitis chronica atrophians skin lesions (strain 1408 c1). Three different experimental conditions have been tested: (1) unstimulated NHDF vs NHDF stimulated by Borrelia strain N40 / (2) unstimulated NHDF vs NHDF stimulated by Borrelia strain Pbre c4 / (3)M-BM- unstimulated NHDF vs NHDF stimulated by Borrelia strain 1408 c1. There is 2 biological replicates for each condition. All NHDF stimulation have been performed in independent experiments.

2012-08-01 | E-GEOD-31740 | biostudies-arrayexpress

Borrelia burgdorferi fitness is constrained during Peromyscus leucopus infection

Project description:The Lyme disease spirochete Borrelia burgdorferi drives a range of acute and chronic maladies in humans and other incidental hosts infected with the pathogen. However, the primary vertebrate reservoir, Peromyscus leucopus appears spared from any symptomology following infection. This has led to a common hypothesis that P. leucopus and B. burgdorferi exist symbiotically: P. leucopus restrain their immune response against the microbe and enable the enzootic cycle while B. burgdorferi avoids causing damage to the host. While aspects of this hypothesis have been tested, the exact interactions that occur between P. leucopus and B. burgdorferi during infection remain largely unknown. Here we utilized an inbred colony of P. leucopus in order to compare B. burgdorferi (B31) fitness in these rodents to the traditional B. burgdorferi murine models—C57BL/6J and C3H/HeN Mus musculus, which develop signs of inflammation akin to human disease. We find that in contrast to our expectations, B. burgdorferi were able to reach much higher burdens in M. musculus, and that the overall kinetics of infection differed between the two rodent species. Surprisingly, we also found that P. leucopus remained infectious to larval Ixodes scapularis for a far shorter period than either M. musculus strain. In line with these observations, we found that P. leucopus does launch a modest but sustained inflammatory response against B. burgdorferi in the skin, which we hypothesize leads to reduced bacterial viability and infectivity in these hosts. These observations provide new insight into the nature of reservoir species and the B. burgdorferi enzootic cycle.

2024-01-03 | GSE244071 | GEO

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