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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...

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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
Descripción
Sumario: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.