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

PLoS Pathogens
Valentina GuerriniMaria Laura Gennaro

Abstract

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.

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Mar 10, 2020·Pathogens and Disease·Elinor Hortle, Stefan H Oehlers
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Datasets Mentioned

BETA
GSE20050

Methods Mentioned

BETA
confocal microscopy
laser capture microdissection
flow cytometry
PCR
density gradient centrifugation
Assay
Protein Assay
fluorescence microscopy

Clinical Trials Mentioned

NCT00816426

Software Mentioned

Leica LAS X
IDEAS
ImageJ
Spot Mask

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