Foam cells are dysfunctional, lipid-laden macrophages associated with chronic inflammation of diverse origin. The long-standing paradigm that foam cells are cholesterol-laden derives from atherosclerosis research. We previously showed that, in tuberculosis, foam cells surprisingly accumulate triglycerides. Here, we utilized bacterial (Mycobacterium tuberculosis), fungal (Cryptococcus neoformans), and human papillary renal cell carcinoma (pRCC) models. We applied mass spectrometry-based imaging to assess the spatial distribution of storage lipids relative to foam-cell-rich areas in lesional tissues, and characterized lipid-laden macrophages generated under corresponding in vitro conditions. The in vivo data were consistent with in vitro findings showing that cryptococcus-infected macrophages accumulated triglycerides, while macrophages exposed to pRCC-conditioned-medium accumulated both triglycerides and cholesterol. Moreover, cryptococcus- and mycobacterium-infected macrophages accumulated triglycerides by different mechanisms. Collectively, our data indicate that the mechanisms of foam cell formation are disease-microenvironment-specific. Since foam cells are potential therapeutic targets, recognizing that their formation is disease-specific opens new biomedical research directions.
Keywords: cryptococcosis; kidney disease; lipid metabolism; papillary renal cell carcinoma; storage lipids; tuberculosis.