title: Essential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages.
abstract: 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.
authors.affiliation: Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanigawa
authors.forename: Yang
authors.initials: Y
authors.lastname: Degang
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akama
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshihara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishido
authors.forename: Masahiko
authors.initials: M
authors.lastname: Makino
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishii
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D015536:Down-Regulation; D006801:Humans; D007918:Leprosy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D050356:Lipid Metabolism; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism* / Q000382:microbiology; D009166:Mycobacterium leprae / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D051195:Toll-Like Receptor 2; D002787:Sterol Esterase