Open 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,
PeiYu Chen,
Karim Lakehal,
Selvakumar Subbian,
Paul E. O’Brien,
Laura E. Via,
Clifton E. Barry,
Véronique Dartois,
Maria Laura Gennaro
Publication year - 2018
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1007223
Subject(s) - foam cell , inflammation , biogenesis , microbiology and biotechnology , mtorc1 , macrophage , mycobacterium tuberculosis , cell , biology , chemistry , immunology , tuberculosis , medicine , in vitro , signal transduction , pathology , pi3k/akt/mtor pathway , biochemistry , gene
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.