**7. Role of foamy macrophages**

After being engulfed by macrophages M tb dys-regulates its lipid metabolism which leads to lipid accumulation within a subset of these macrophages giving them a characteristic foamy phenotype. The lipid packed foamy macrophages have been associated with several chronic disease conditions such as atherosclerosis and during infections with persistent intracellular pathogens e.g. M Tb, Chlamydia and Toxoplasma (Kalayoglu MV and Byrne GI, 1998; Portugal LR et al., 2008; Galkina E and Ley K, 2009). Triglycerides, phospholipids and cholesterol constitute the low density lipo-proteins (LDL) and in foamy macrophages the influx and efflux of LDLs is dys-regulated (Russell DG, et al., 2009). Cholesterol gets esterified when the macrophage attains foamy phenotype and is retained as lipid droplets (Russell DG et al., 2009). Recently it has been shown that triacylglycerols (TAG) of M Tb are derived from host TAG and are imported by the bacterium for its lipid synthesis (Daniel J et al., 2011). M tb incorporates host derived lipids directly into its own pool and the accumulation of neutral lipids by the M tb leads to its lipid fastness (Daniel J et al., 2011).

It is shown that pathogenic mycobacteria synthesize oxygenated mycolic acids which induce foamy cell formation of the macrophages (Peyron P et al., 2008) but this might not hold true under hypoxic conditions (Daniel J et al., 2011). Peyron P et al., 2008 have shown that these lipid droplets serve as nutritional source to the pathogen and help in its non-replicative life cycle and persistence. One recent report also suggested that mycobacterium prevents lipolysis by interfering with the host lipid metabolic pathways, which leads to lipid accumulation inside the macrophage (Singh V et al., 2012). These lipids serve as a source of nutrition and help the pathogen in its dormant lifestyle. The specific presence of foamy macrophages in the necrotic regions has been suggested that they play crucial role in necrosis and hence in spreading of the bacterium (Peyron P et al., 2008). Although macrophages are the frontline innate immune cells, it is clear that their foamy phenotype helps the pathogen in establishing persistent infection and the host innate and adaptive immune response is no more able to eliminate the pathogen once it happens. Thus the ideal way to target the pathogen is before the establishment of the foamy phenotype of the macrophages harbouring the M Tb.
