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

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly u...

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Bibliographic Details
Published in:PLoS biology 2021-01, Vol.19 (1), p.e3001062-e3001062
Main Authors: Barriales, Diego, Martín-Ruiz, Itziar, Carreras-González, Ana, Montesinos-Robledo, Marta, Azkargorta, Mikel, Iloro, Ibon, Escobés, Iraide, Martín-Mateos, Teresa, Atondo, Estibaliz, Palacios, Ainhoa, Gonzalez-Lopez, Monika, Bárcena, Laura, Cortázar, Ana R, Cabrera, Diana, Peña-Cearra, Ainize, van Liempd, Sebastiaan M, Falcón-Pérez, Juan M, Pascual-Itoiz, Miguel A, Flores, Juana María, Abecia, Leticia, Pellon, Aize, Martínez-Chantar, Maria Luz, Aransay, Ana M, Pascual, Alberto, Elortza, Felix, Berra, Edurne, Lavín, José Luis, Rodríguez, Héctor, Anguita, Juan
Format: Article
Language:English
Subjects:
Antibiotics
Biology and Life Sciences
Borreliosis
Cardiomyopathy
Carditis
Dilated cardiomyopathy
Endocarditis
Epigenetics
Fatty acids
Genes
Heart
Heart diseases
Immunological memory
Infections
Inflammation
Long term memory
Macrophages
Medicine and Health Sciences
Memory cells
Metabolism
Metabolites
Microorganisms
Monocytes
Myocardial infarction
Myocarditis
Ontology
Pancarditis
Pathogens
Pericarditis
Phagocytosis
Principal components analysis
Proteins
Regulatory mechanisms (biology)
Spirochetes
Transcription
Variance analysis
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Summary:Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, 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 down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the 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.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3001062