Cargando…

Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific

Foam cells are lipid-laden macrophages that contribute to the inflammation and tissue damage associated with many chronic inflammatory disorders. Although foam cell biogenesis has been extensively studied in atherosclerosis, how these cells form during a chronic infectious disease such as tuberculos...

Descripción completa

Detalles Bibliográficos
Autores principales: Guerrini, Valentina, Prideaux, Brendan, Blanc, Landry, Bruiners, Natalie, Arrigucci, Riccardo, Singh, Sukhwinder, Ho-Liang, Hsin Pin, Salamon, Hugh, Chen, Pei-Yu, Lakehal, Karim, Subbian, Selvakumar, O’Brien, Paul, Via, Laura E., Barry, Clifton E., Dartois, Véronique, Gennaro, Maria Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117085/
https://www.ncbi.nlm.nih.gov/pubmed/30161232
http://dx.doi.org/10.1371/journal.ppat.1007223
_version_ 1783351702574858240
author Guerrini, Valentina
Prideaux, Brendan
Blanc, Landry
Bruiners, Natalie
Arrigucci, Riccardo
Singh, Sukhwinder
Ho-Liang, Hsin Pin
Salamon, Hugh
Chen, Pei-Yu
Lakehal, Karim
Subbian, Selvakumar
O’Brien, Paul
Via, Laura E.
Barry, Clifton E.
Dartois, Véronique
Gennaro, Maria Laura
author_facet Guerrini, Valentina
Prideaux, Brendan
Blanc, Landry
Bruiners, Natalie
Arrigucci, Riccardo
Singh, Sukhwinder
Ho-Liang, Hsin Pin
Salamon, Hugh
Chen, Pei-Yu
Lakehal, Karim
Subbian, Selvakumar
O’Brien, Paul
Via, Laura E.
Barry, Clifton E.
Dartois, Véronique
Gennaro, Maria Laura
author_sort Guerrini, Valentina
collection PubMed
description Foam cells are lipid-laden macrophages that contribute to the inflammation and tissue damage associated with many chronic inflammatory disorders. Although foam cell biogenesis has been extensively studied in atherosclerosis, how these cells form during a chronic infectious disease such as tuberculosis is unknown. Here we report that, unlike the cholesterol-laden cells of atherosclerosis, foam cells in tuberculous lung lesions accumulate triglycerides. Consequently, the biogenesis of foam cells varies with the underlying disease. In vitro mechanistic studies showed that triglyceride accumulation in human macrophages infected with Mycobacterium tuberculosis is mediated by TNF receptor signaling through downstream activation of the caspase cascade and the mammalian target of rapamycin complex 1 (mTORC1). These features are distinct from the known biogenesis of atherogenic foam cells and establish a new paradigm for non-atherogenic foam cell formation. Moreover, they reveal novel targets for disease-specific pharmacological interventions against maladaptive macrophage responses.
format Online
Article
Text
id pubmed-6117085
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-61170852018-09-16 Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific Guerrini, Valentina Prideaux, Brendan Blanc, Landry Bruiners, Natalie Arrigucci, Riccardo Singh, Sukhwinder Ho-Liang, Hsin Pin Salamon, Hugh Chen, Pei-Yu Lakehal, Karim Subbian, Selvakumar O’Brien, Paul Via, Laura E. Barry, Clifton E. Dartois, Véronique Gennaro, Maria Laura PLoS Pathog Research Article Foam cells are lipid-laden macrophages that contribute to the inflammation and tissue damage associated with many chronic inflammatory disorders. Although foam cell biogenesis has been extensively studied in atherosclerosis, how these cells form during a chronic infectious disease such as tuberculosis is unknown. Here we report that, unlike the cholesterol-laden cells of atherosclerosis, foam cells in tuberculous lung lesions accumulate triglycerides. Consequently, the biogenesis of foam cells varies with the underlying disease. In vitro mechanistic studies showed that triglyceride accumulation in human macrophages infected with Mycobacterium tuberculosis is mediated by TNF receptor signaling through downstream activation of the caspase cascade and the mammalian target of rapamycin complex 1 (mTORC1). These features are distinct from the known biogenesis of atherogenic foam cells and establish a new paradigm for non-atherogenic foam cell formation. Moreover, they reveal novel targets for disease-specific pharmacological interventions against maladaptive macrophage responses. Public Library of Science 2018-08-30 /pmc/articles/PMC6117085/ /pubmed/30161232 http://dx.doi.org/10.1371/journal.ppat.1007223 Text en © 2018 Guerrini et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Guerrini, Valentina
Prideaux, Brendan
Blanc, Landry
Bruiners, Natalie
Arrigucci, Riccardo
Singh, Sukhwinder
Ho-Liang, Hsin Pin
Salamon, Hugh
Chen, Pei-Yu
Lakehal, Karim
Subbian, Selvakumar
O’Brien, Paul
Via, Laura E.
Barry, Clifton E.
Dartois, Véronique
Gennaro, Maria Laura
Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
title Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
title_full Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
title_fullStr Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
title_full_unstemmed Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
title_short Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
title_sort storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117085/
https://www.ncbi.nlm.nih.gov/pubmed/30161232
http://dx.doi.org/10.1371/journal.ppat.1007223
work_keys_str_mv AT guerrinivalentina storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT prideauxbrendan storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT blanclandry storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT bruinersnatalie storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT arrigucciriccardo storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT singhsukhwinder storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT holianghsinpin storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT salamonhugh storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT chenpeiyu storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT lakehalkarim storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT subbianselvakumar storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT obrienpaul storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT vialaurae storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT barrycliftone storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT dartoisveronique storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific
AT gennaromarialaura storagelipidstudiesintuberculosisrevealthatfoamcellbiogenesisisdiseasespecific