02346nas a2200337   4500000000100000008004100001260001300042653002000055653001100075653001200086653002100098653001600119653002500135653001500160653002000175653002500195100001500220700001300235700001600248700001200264700001600276700001300292700001300305700001200318700001300330245013500343300001100478490000700489520149800496022001401994       2012                            d  c2012 May10aDown-Regulation10aHumans10aleprosy10aLipid Metabolism10aMacrophages10aMycobacterium leprae10aPhagosomes10aSterol Esterase10aToll-Like Receptor 21 aTanigawa K1 aDegang Y1 aKawashima A1 aAkama T1 aYoshihara A1 aIshido Y1 aMakino M1 aIshii N1 aSuzuki K00aEssential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages.  a285-910 v523 a<p>Mycobacterium leprae (M. leprae), the causative agent of leprosy, parasitizes within the foamy or enlarged phagosome of macrophages where rich lipids accumulate. Although the mechanisms for lipid accumulation in the phagosome have been clarified, it is still unclear how such large amounts of lipids escape degradation. To further explore underlying mechanisms involved in lipid catabolism in M. leprae-infected host cells, we examined the expression of hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization and lipolysis, in human macrophage THP-1 cells. We found that infection by live M. leprae significantly suppressed HSL expression levels. This suppression was not observed with dead M. leprae or latex beads. Macrophage activation by peptidoglycan (PGN), the ligand for toll-like receptor 2 (TLR2), increased HSL expression; however, live M. leprae suppressed this increase. HSL expression was abolished in the slit-skin smear specimens from patients with lepromatous and borderline leprosy. In addition, the recovery of HSL expression was observed in patients who experienced a lepra reaction, which is a cell-mediated, delayed-type hypersensitivity immune response, or in patients who were successfully treated with multi-drug therapy. These results suggest that M. leprae suppresses lipid degradation through inhibition of HSL expression, and that the monitoring of HSL mRNA levels in slit-skin smear specimens may be a useful indicator of patient prognosis.</p>  a1096-1208