Heterogeneity of foam cell biogenesis across diseases

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. ### Competing Interest Statement The authors have declared no competing interest. * CE : cholesteryl esters H&E : hematoxylin and eosin MALDI : matrix-assisted laser desorption/ionization mass spectrometry MDM : monocyte-derived macrophages pRCC : papillary renal cell carcinoma TAG : triglycerides.