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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.
This article was published in the following journal.
Name: PLoS pathogens
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A family of vertebrate and insect lipid droplet associated proteins. They consist of a conserved N-terminal PAT domain (an alpha-helical region of about 110 amino acids), an 11-mer repeat region, and lipid-binding hydrophobic regions or 4-helix bundles near their C-termini. Perilipins transiently or constitutively localize to LIPID DROPLETS in ADIPOCYTES and FOAM CELLS, especially in regions adjacent to the PLASMA MEMBRANE and ENDOPLASMIC RECTICULUM. They are critical for lipid droplet synthesis and homeostasis as well as the regulation of lipid metabolism. Genetic variations in perilipins are associated with ATHEROSCLEROSIS; OBESITY; and DIABETES MELLITUS.
A perilipin that is expressed by many different cell types. It binds FATTY ACIDS and CHOLESTEROL, stabilizes TRIGLYCERIDES, and localizes to both the surface and hydrophobic core of LIPID DROPLETS, as well as the ENDOPLASMIC RECTICULUM and PLASMA MEMBRANE in MACROPHAGES. It also plays a central role in the biogenesis of lipid droplets and FOAM CELLS and is highly expressed by macrophages at atherosclerotic lesions in human arteries along with the INFLAMMATION markers TNF-ALPHA; MCP-1 RECEPTOR; and IL-6.
A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.
A lipid droplet protein that is expressed primarily by ADIPOCYTES of WHITE ADIPOSE TISSUE and BROWN ADIPOSE TISSUE. It co-localizes with MACROPHAGES and FOAM CELLS of artherosclerotic lesions and stabilizes LIPID DROPLETS by inhibiting HORMONE SENSITIVE LIPASE. It may also protect TRIGLYCERIDES against hydrolysis within the PLASMA MEMBRANE and modulate CHOLESTEROL ESTER HYDROLASE activity.
Dynamic cytoplasmic organelles found in almost all cells. They consist of a central core of LIPIDS surrounded by a phospholipid monolayer studded with surface proteins, and are involved in LIPID METABOLISM and storage.
Tuberculosis (TB) is an infectious disease caused by bacteria belonging to the Mycobacterium tuberculosis complex. Over nine million new cases of TB, and nearly two million deaths from TB, are estimated to occur around the world every year, and new inf...