Foam Cell Macrophages in Tuberculosis

Abstract

Mycobacterium tuberculosis infects primarily macrophages in the lungs. Infected macrophages are surrounded by other immune cells in well organised structures called granulomata. As part of the response to TB, a type of macrophage loaded with lipid droplets arises which we call Foam cell macrophages. They are macrophages filled with lipid laden droplets, which are synthesised in response to increased uptake of extracellular lipids, metabolic changes and infection itself. They share the appearance with atherosclerosis foam cells, but their lipid contents and roles are different. In fact, lipid droplets are immune and metabolic organelles with emerging roles in Tuberculosis. Here we discuss lipid droplet and foam cell formation, evidence regarding the inflammatory and immune properties of foam cells in TB, and address gaps in our knowledge to guide further research.

Keywords: Mycobacterium; foam cells; lipid droplets; macrophage; tuberculosis.

Figure 1

Foam cells in TB. (A) Lipid droplet synthesis in macrophages can be triggered by external and internal stimuli. Extrinsic complex sources of lipids include phagocytosis of apoptotic or necrotic cells, or endocytosis, pinocytosis and receptor mediated uptake of lipoproteins. Simpler fatty acids can be transported by specialised machineries in the cell. Lysosomal activity and autophagy contribute to the degradation of accumulated lipid remnants in the cell to avoid lipotoxicity. Cytokines, hormones, growth factors and metabolic changes such as variations of glucose level, induce enzymes and proteins important for lipid synthesis and droplet stability. (B) Although there is no consensus, some markers appear repeatedly in Foam cell literature. Foam cells have been shown to have increased scavenger receptors- CD36, CD163, TNF-α/TRAF1,2, the inflammatory cytokine IL-6 and the inflammasome dependent IL-1β. The checkpoint inhibitor PDL1 has been shown as increased while the antigen presentation related HLA-DR as decreased. Upregulated markers are colour coded in red and downregulated in green. These and other markers can guide needed translational histological studies on foam cells in multiple species and cell line models. It is early to ascertain the true nature of foam cells in TB, and more research in primary models is necessary since THP1 and primary macrophages behave differently. See text for references.