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open-access-imgOpen AccessStorage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific
Author(s)
Valentina Guerrini,
Brendan Prideaux,
Landry Blanc,
Natalie Bruiners,
Riccardo Arrigucci,
Sukhwinder Singh,
Hsin Pin Ho-Liang,
Hugh Salamon,
Pei-Yu Chen,
Karim Lakehal,
Selvakumar Subbian,
Paul O'Brien,
Laura E. Via,
Clifton E. Barry,
Véronique Dartois,
Maria Laura Gennaro
Publication year2018
Publication title
plos pathogens
Resource typeJournals
PublisherPublic Library of Science
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.
Subject(s)biochemistry , biogenesis , biology , cell , chemistry , cholesterol , disease , foam cell , gene , genetics , lipoprotein , medicine , microbiology and biotechnology , mycobacterium tuberculosis , pathology , tuberculosis
Language(s)English
SCImago Journal Rank3.719
H-Index206
ISSN1553-7366
DOI10.1371/journal.ppat.1007223

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