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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3001062 |
| _version_ | 1831729699850551296 |
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| author | Diego Barriales Itziar Martín-Ruiz Ana Carreras-González Marta Montesinos-Robledo Mikel Azkargorta Ibon Iloro Iraide Escobés Teresa Martín-Mateos Estibaliz Atondo Ainhoa Palacios Monika Gonzalez-Lopez Laura Bárcena Ana R Cortázar Diana Cabrera Ainize Peña-Cearra Sebastiaan M van Liempd Juan M Falcón-Pérez Miguel A Pascual-Itoiz Juana María Flores Leticia Abecia Aize Pellon Maria Luz Martínez-Chantar Ana M Aransay Alberto Pascual Felix Elortza Edurne Berra José Luis Lavín Héctor Rodríguez Juan Anguita |
| author_facet | Diego Barriales Itziar Martín-Ruiz Ana Carreras-González Marta Montesinos-Robledo Mikel Azkargorta Ibon Iloro Iraide Escobés Teresa Martín-Mateos Estibaliz Atondo Ainhoa Palacios Monika Gonzalez-Lopez Laura Bárcena Ana R Cortázar Diana Cabrera Ainize Peña-Cearra Sebastiaan M van Liempd Juan M Falcón-Pérez Miguel A Pascual-Itoiz Juana María Flores Leticia Abecia Aize Pellon Maria Luz Martínez-Chantar Ana M Aransay Alberto Pascual Felix Elortza Edurne Berra José Luis Lavín Héctor Rodríguez Juan Anguita |
| author_sort | Diego Barriales |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T07:17:37Z |
| format | Article |
| id | doaj.art-65e28a5181ec4bb4abc1d89b6cd6cf00 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-21T07:17:37Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-65e28a5181ec4bb4abc1d89b6cd6cf002022-12-21T19:11:51ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852021-01-01191e300106210.1371/journal.pbio.3001062Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.Diego BarrialesItziar Martín-RuizAna Carreras-GonzálezMarta Montesinos-RobledoMikel AzkargortaIbon IloroIraide EscobésTeresa Martín-MateosEstibaliz AtondoAinhoa PalaciosMonika Gonzalez-LopezLaura BárcenaAna R CortázarDiana CabreraAinize Peña-CearraSebastiaan M van LiempdJuan M Falcón-PérezMiguel A Pascual-ItoizJuana María FloresLeticia AbeciaAize PellonMaria Luz Martínez-ChantarAna M AransayAlberto PascualFelix ElortzaEdurne BerraJosé Luis LavínHéctor RodríguezJuan AnguitaLyme 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.https://doi.org/10.1371/journal.pbio.3001062 |
| spellingShingle | Diego Barriales Itziar Martín-Ruiz Ana Carreras-González Marta Montesinos-Robledo Mikel Azkargorta Ibon Iloro Iraide Escobés Teresa Martín-Mateos Estibaliz Atondo Ainhoa Palacios Monika Gonzalez-Lopez Laura Bárcena Ana R Cortázar Diana Cabrera Ainize Peña-Cearra Sebastiaan M van Liempd Juan M Falcón-Pérez Miguel A Pascual-Itoiz Juana María Flores Leticia Abecia Aize Pellon Maria Luz Martínez-Chantar Ana M Aransay Alberto Pascual Felix Elortza Edurne Berra José Luis Lavín Héctor Rodríguez Juan Anguita Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. PLoS Biology |
| title | Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. |
| title_full | Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. |
| title_fullStr | Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. |
| title_full_unstemmed | Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. |
| title_short | Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. |
| title_sort | borrelia burgdorferi infection induces long term memory like responses in macrophages with tissue wide consequences in the heart |
| url | https://doi.org/10.1371/journal.pbio.3001062 |
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