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

• DOI: 10.1371/journal.pbio.3001062
• Publication Date: 2021-01-04T19:13:15Z
• Authors: Diego Barriales; Itziar Martín-Ruiz; Ana Carreras-Gonz...; Marta Montesinos-...; Mikel Azkargorta; Ibon Iloro; Iraide Escobés; Teresa Martín-Mateos; Estibaliz Atondo; Ainhoa Palacios; Monika Gonzalez-L...; Laura Bárcena; Ana R. Cortázar; Diana Cabrera; Ainize Peña-Cearra; Sebastiaan M. van...; Juan M. Falcón-Pérez; Miguel A. Pascual...; Juana María Flores; Leticia Abecia; Aize Pellon; Maria Luz Martíne...; Ana M. Aransay; Alberto Pascual; Felix Elortza; Edurne Berra; José Luis Lavín; Héctor Rodríguez; Juan Anguita
• Keywords: 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

Lyme carditis is an extracutaneous manifestation of disease characterized by episodes atrioventricular block varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over course infection are poorly understood. Here, we identify broad transcriptomic proteomic in heart during that reveal a profound down-regulation mitochondrial components. We also describe long-term functional modulation macrophages exposed live bacteria, augmented glycolytic output, increased spirochetal binding internalization, reduced inflammatory responses. In vitro, glycolysis inhibition reduces production tumor necrosis factor (TNF) memory macrophages, whereas vivo, it produces reversion phenotype, recovery tissue components, decreased inflammation burdens. These results show B . induces long-term, memory-like responses tissue-wide consequences amenable be manipulated vivo.