Low-density lipoprotein cholesterol drives multinucleated giant cell formation in response to mycobacterium bovis Bacille Calmette-Guérin

Macrophages play a central role in tuberculosis, both in bacterial persistence and tissue pathology. Body weight and a dysregulated lipid metabolism profoundly affect disease progression and survival. Yet, the relationship between lipid metabolism and mycobacterial immunity is still poorly understood. Accordingly, this study investigated the influence of cholesterol and lipoproteins on macrophage responses to mycobacteria, in particular the formation of multinucleated giant cells (MGC), which are key components of granulomas and involved in the containment of mycobacteria. We found that low-density lipoprotein (LDL) cholesterol was essential for the transformation of macrophage progenitors into MGCs in vitro, independent of the oxidation status. In contrast to these direct lipid effects on macrophage transformation, a lipid-rich diet to mice, which is known to elevate cholesterol levels in the blood, did not prime the MGC forming potential of bone-marrow progenitor cells. In conclusion, LDL promotes the mycobacteria-specific macrophage transformation, however, this effect appears to depend on tissue lipid availability rather than priming in the bone marrow.