Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart
Male
QH301-705.5
Economía
Mice
03 medical and health sciences
Animals
Humans
Macrófagos
Myocytes, Cardiac
Biology (General)
Cells, Cultured
Inflammation
Lyme Disease
0303 health sciences
Infecciones
Spirochetes
Corazón
Enfermedad de Lyme
Macrophages
Heart
Endocarditis, Bacterial
Macrophage Activation
Gene regulation
3. Good health
Mice, Inbred C57BL
Glucólisis
HEK293 Cells
RAW 264.7 Cells
Borrelia burgdorferi
Cytokines
Miocarditis
Cardiomiopatías
Female
Bacterias
Cardiomyopathies
Glycolysis
Immunologic Memory
Research Article
DOI:
10.1371/journal.pbio.3001062
Publication Date:
2021-01-04T19:13:15Z
AUTHORS (29)
ABSTRACT
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.
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CITATIONS (13)
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