Related Experiment Video
Updated: Jun 27, 2026
A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces
Published on: January 7, 2020
Expression of adipose differentiation-related protein (ADRP) and perilipin in macrophages infected with Mycobacterium
Kazunari Tanigawa1, Koichi Suzuki, Kazuaki Nakamura
1Department of Bioregulation, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan.
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.
Insights
Live Mycobacterium leprae manipulates host cells to accumulate lipids within phagosomes, using proteins like ADRP and perilipin to create a nutrient-rich environment for its survival in leprosy.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Leprosy pathogenesis involves Mycobacterium leprae residing in host histiocytes within lipid-rich phagosomes.
- The mechanisms driving phagosomal lipid accumulation, crucial for M. leprae survival, are not fully understood.
- Lipid droplet-associated proteins (e.g., ADRP, perilipin) are known to regulate lipid metabolism in macrophages.
Purpose of the Study:
- To investigate the role of ADRP and perilipin in M. leprae-induced lipid accumulation within phagosomes.
- To elucidate how M. leprae manipulates host cell machinery to facilitate its intracellular survival.
Main Methods:
- Immunohistochemical analysis of skin biopsy specimens from lepromatous leprosy patients.
- Cell culture experiments using THP-1 cells infected with live or dead M. leprae and latex beads.
- Assessment of ADRP and perilipin expression following M. leprae infection and stimulation with peptidoglycan (TLR2 ligand).
Main Results:
- ADRP and perilipin were found on the phagosomal membrane containing M. leprae in leprosy lesions.
- M. leprae infection, but not dead bacilli or beads, induced sustained ADRP expression in THP-1 cells.
- M. leprae infection counteracted the suppressive effect of peptidoglycan on ADRP/perilipin expression.
Conclusions:
- Live M. leprae actively induces and sustains ADRP/perilipin expression.
- This induction promotes lipid accumulation within phagosomes, creating a favorable niche for M. leprae.
- M. leprae employs sophisticated mechanisms to exploit host lipid metabolism for its intracellular survival.
