Expression of adipose differentiation-related protein (ADRP) and perilipin in macrophages infected with Mycobacterium leprae.
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.
Tanigawa
Kazunari
K
Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.
Suzuki
Koichi
K
Nakamura
Kazuaki
K
Akama
Takeshi
T
Kawashima
Akira
A
Wu
Huhehasi
H
Hayashi
Moyuru
M
Takahashi
Shin-Ichiro
S
Ikuyama
Shoichiro
S
Ito
Tetsuhide
T
Ishii
Norihisa
N
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
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