Foam Cells: One Size Doesn’t Fit All

Foam cells can exhibit impaired immune functions and contribute to the pathogenesis of various diseases by inducing inflammation and tissue damage, regardless of pathological context. They also facilitate pathogen survival in infectious diseases. Biogenesis and storage lipid composition of foam cells depend on the immunopathological context and are disease specific. The cholesterol-rich foam cells formed during atherosclerosis and the triglyceride-rich foam cells found in tuberculosis can be taken to represent two different paradigms of foam cell formation. Foam cells offer a novel putative target for pharmacological attack against disease, since they are often implicated in pathogenesis and disease progression. Chronic inflammation in many infectious and metabolic diseases, and some cancers, is accompanied by the presence of foam cells. These cells form when the intracellular lipid content of macrophages exceeds their capacity to maintain lipid homeostasis. Concurrently, critical macrophage immune functions are diminished. Current paradigms of foam cell formation derive from studies of atherosclerosis. However, recent studies indicate that the mechanisms of foam cell biogenesis during tuberculosis differ from those operating during atherogenesis. Here, we review how foam cell formation and function vary with disease context. Since foam cells are therapeutic targets in atherosclerosis, further research on the disease-specific mechanisms of foam cell biogenesis and function is needed to explore the therapeutic consequences of targeting these cells in other diseases. Chronic inflammation in many infectious and metabolic diseases, and some cancers, is accompanied by the presence of foam cells. These cells form when the intracellular lipid content of macrophages exceeds their capacity to maintain lipid homeostasis. Concurrently, critical macrophage immune functions are diminished. Current paradigms of foam cell formation derive from studies of atherosclerosis. However, recent studies indicate that the mechanisms of foam cell biogenesis during tuberculosis differ from those operating during atherogenesis. Here, we review how foam cell formation and function vary with disease context. Since foam cells are therapeutic targets in atherosclerosis, further research on the disease-specific mechanisms of foam cell biogenesis and function is needed to explore the therapeutic consequences of targeting these cells in other diseases. lesions of the arterial intima that occur during atherosclerosis. series of regulated processes for the transfer of intracellular components (molecules and organelles) to lysosomes for degradation. atherosclerotic narrowing of the carotid artery. lipid-rich necrotic material of ‘cheese-like’ appearance that occupies the center of the necrotizing tuberculous granuloma. infectious disease caused by the parasite Trypanosoma cruzi that is transmitted to animals and humans by insect vectors. release into an adjacent airway of the liquefying necrotic material at the center of a necrotic tuberculous granuloma; it facilitates infection transmission. highly regulated clearance of apoptotic cells by phagocytes that maintains homeostasis, prevents autoimmune diseases, and resolves inflammatory insults. bioactive signaling lipids derived from arachidonic acid and related polyunsaturated fatty acids; they act locally to regulate a variety of homeostatic and inflammatory processes. cell-derived membranous structures originating from the endosomal system (exosomes) or shed from the plasma membrane (microvesicles); they represent a mechanism for intercellular communication. progressive decrease in thickness of the atheroma fibrous cap in advanced lesions; it may lead to plaque rupture and thrombosis. clusters of immune cells forming in response to an infectious or noninfectious (foreign) agent. infection caused by the inhalation of spores produced by the fungus Histoplasma capsulatum. sample preparation technique that enables isolation of subpopulations of tissue cells by using microscopic visualization and laser-based dissection. form of autophagy in which intracellular lipid droplets are degraded following the fusion of lipid droplet-containing autophagosomes with lysosomes. inducing the classically activated M1 proinflammatory phenotype of macrophages. protein kinase complex that links nutrient sensing to regulation of cellular metabolism. vacuole derived from the host plasma membrane within which parasites of the phylum Apicomplexa reside and replicate. recognize conserved pathogen-associated molecular structures (PAMPs), and have key roles in innate immunity. protein located on the surface of lipid droplets in eukaryotic cells; it is the key regulator of storage lipid lipolysis. member of the lipid-sensing nuclear receptor family that acts as a transcriptional regulator of cellular lipid and glucose metabolism, cell proliferation and differentiation, and inflammation. It forms heterodimers with the retinoid X receptor and binds to PPAR response elements located in the promoter region of target genes. induces the accumulation of cytoplasmic lipid droplets. receptors that bind and internalize a variety of ligands, including endogenous and modified host-derived molecules and microbial pathogens. They are involved in the clearance of modified lipoproteins by phagocytes during atherosclerosis and in the regulation of innate immune responses through the recognition of pathogen-associated molecular patterns. transcription factor that regulates cellular lipogenesis and lipid homeostasis. nuclear receptor that transcriptionally regulates cell metabolism, replication, and death. It is transactivated by fatty acid metabolites and thiazolidinedione compounds. It binds hormone-response elements located in the promoter region of target genes. microbial-sensing proteins expressed by immune cells. Various families of TLRs recognize specific PAMPs and trigger intracellular signaling events that regulate activation of innate and adaptive immunity.