title: Expression of adipose differentiation-related protein (ADRP) and perilipin in macrophages infected with Mycobacterium leprae.
abstract: Mycobacterium leprae survives and replicates within a lipid droplet stored in the enlarged phagosome of histiocytes, a typical feature of lepromatous leprosy that is thought to be an important nutrient source for the bacillus. However, the underlying mechanisms by which lipids accumulate within phagosomes remain unclear. Recently, it was revealed that the lipid droplet-associated proteins, including ADRP and perilipin, play essential roles in lipid accumulation in adipocytes or macrophages. Therefore, we attempted to examine the role of these proteins in leprosy pathogenesis. ADRP and perilipin localized to the phagosomal membrane, which contains M. leprae in skin biopsy specimens of lepromatous leprosy. ADRP expression was transiently increased after phagocytosis in THP-1 cells. However, high levels of ADRP expression persisted only when live M. leprae, but not dead bacilli or latex beads, was added. Furthermore, although peptidoglycan, a Toll-like receptor 2 ligand, suppressed the expression levels of ADRP and perilipin, M. leprae infection inhibited this suppression. These results suggest that live M. leprae has the ability to actively induce and support ADRP/perilipin expression to facilitate the accumulation of lipids within the phagosome and to further maintain a suitable environment for the intracellular survival within the macrophage.
authors.affiliation: Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanigawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akama
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Huhehasi
authors.initials: H
authors.lastname: Wu
authors.forename: Moyuru
authors.initials: M
authors.lastname: Hayashi
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ikuyama
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D015440:Leprosy, Lepromatous / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009166:Mycobacterium leprae / Q000472:pathogenicity*; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins; C000602983:Plin2 protein, mouse; D012333:RNA, Messenger