Heterogeneity of foam cell biogenesis across diseases

Foam cells are dysfunctional, lipid-laden macrophages associated with chronic inflammation of infectious and non-infectious origin. To test the hypothesis that foam cell biogenesis is disease-specific, we compared bulk transcriptomics data obtained by RNA seq in human monocyte derived macrophages (MDM) subjected to two types of infections in vitro. One was with Mycobacterium tuberculosis and the other with Cryptococcus neoformans. We also exposed MDM to cell-free conditioned medium from cultures of the ACHN cell line, which is derived from a human renal cell carcinoma, to study foam cell formation in the context of papillary renal cell carcinoma (pRCC). We found that, with both infections, the accumulation of TAG results from decreased oxidative phosphorylation, increased glycolysis, increased lipid biosynthesis, and decreased lipid catabolism. However, the molecular modalities of Overall design: The differential expression between sample classes (treated vs non treated for each condition) was tested with coincident extreme ranks in numerical observations (CERNO) for metabolism-related Gene Ontology gene sets. The Benjamini–Hochberg method was used to calculate the false discovery rate (FDR). Gene sets (pathways) were identified at a cutoff false discovery rate of 0.05. To identify pathways underlying neutral lipid accumulation, we analyzed the Gene Ontology (GO) annotations related to metabolic processes. In addition, to conduct gene-level analyses, genes in differentially expressed metabolism-related Gene Ontology gene sets having FDR < 0.05 were selected based on individual p value (p << 0.05) and ranked by log2 fold change (treated vs non-treated in each condition) and number of occurrences in the differentially expressed gene sets.