Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart
Open Access
- 4 January 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS Biology
- Vol. 19 (1) , e3001062
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.Keywords
Funding Information
- Ministerio de Ciencia, Innovación y Universidades (RTI2018-096494-B-100)
- Ministerio de Ciencia, Innovación y Universidades (SAF2015-65327-R)
- Ministerio de Ciencia, Innovación y Universidades (BFU2016-76872-R)
- Ministerio de Ciencia, Innovación y Universidades (AGL2017-86757-R)
- Ministerio de Ciencia, Innovación y Universidades (SAF2017-87301-R)
- Ministerio de Ciencia, Innovación y Universidades (SAF2015-64111-R)
- Ministerio de Ciencia, Innovación y Universidades (SAF2015-73549-JIN)
- Ministerio de Ciencia, Innovación y Universidades (RYC-2013-13666)
- Instituto de Salud Carlos III (PIE13/0004)
- Berrikuntza + Ikerketa + Osasuna Eusko Fundazioa (2015111117)
- Berrikuntza + Ikerketa + Osasuna Eusko Fundazioa (BIO15/CA/016/BS)
- Agencia de Innovación y Desarrollo de Andalucía (P12-CTS-2232)
- Ministerio de Ciencia, Innovación y Universidades (SEV-2016-0644)
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