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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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			Action	DRS
	SRR11973400.fastq.gz	Fastqsanger.gz
	SRR11973401.fastq.gz	Fastqsanger.gz
	SRR11973402.fastq.gz	Fastqsanger.gz
	SRR11973403.fastq.gz	Fastqsanger.gz
	SRR11973404.fastq.gz	Fastqsanger.gz

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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.

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Project description:Lyme disease is a result from an infection by the spirochete Borrelia burgdorferi, and is the leading vector-borne disease in North America. Due to the genomic and proteomic variability of different B. burgdorferi isolates, the study and further comparison of their proteome is key to understand the biology and infectivity of these spirochetes. Mass spectrometry-based proteomics was used to assemble peptide datasets of laboratory isolates B31, MM1, B31-ML23, and the infective isolates B31-5A4, B31-A3, and 297, as well as other public datasets, and is publicly available as the Borrelia PeptideAtlas (http://www.peptideatlas.org/builds/borrelia/). These datasets include information on total proteome, secretome, and membrane proteome of the B. burgdorferi.

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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.

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