Heterogeneity of foam cell biogenesis across diseases.

Chronic inflammatory states of infectious and non-infectious etiology are associated with dysfunctional immune responses. Primary contributors are foam cells, lipid-laden macrophages exhibiting impaired or pathogenic immune functions. In contrast with the long-standing paradigm derived from atherosclerosis in which foam cells are cholesterol-laden, our work demonstrates that foam cells are heterogeneous. Utilizing bacterial, fungal, and cancer models, we show that foam cells may accumulate various storage lipids (triglycerides and/or cholesteryl esters) by mechanisms that depend on disease-specific microenvironments. Thus, we present a new framework for foam cell biogenesis in which the atherosclerosis paradigm represents only a specific case. Since foam cells are a potential therapeutic target, understanding their mechanisms of biogenesis will provide knowledge needed for novel therapeutic approaches.