Rab7 controls lipid droplet-phagosome association during mycobacterial infection |
| |
| Affiliation: | 1. Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA;2. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA;3. Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA;1. Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA;1. Host-Pathogen Interactions In Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK;2. Mycobacterial Systems Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK;3. Department of Biosciences, University of Oslo, Blindernveien 31, 0371 Oslo, Norway;4. Tuberculosis Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK;5. Department of Immunology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany;6. Radboud Institute for Molecular Life Sciences (RIMLS), Geert Grooteplein 26/28, Nijmegen 6525 GA, the Netherlands;1. Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germany;2. Department of Structural Cell Biology, Institute for Cell Biology and Neuroscience, Goethe University Frankfurt, Max-von-Laue-Str. 13, 60438 Frankfurt, Germany;3. Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany;1. Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway;2. Faculty of Biosciences and Aquaculture, Nord University, Steinkjer, Norway;3. VITAS AS, Oslo, Norway;4. Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;5. Institute of Clinical Medicine, University of Oslo, Oslo, Norway;6. Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway;7. Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, MD, USA;8. The Norwegian Transgenic Center, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;1. Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein Zuid 32, 6525 GA, Nijmegen, The Netherlands;2. Department of Anesthesiology, Pain and Palliative Medicine, Radboud UMC, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands |
| |
| Abstract: | Lipid droplets (LDs) are organelles that have multiple roles in inflammatory and infectious diseases. LD act as essential platforms for immunometabolic regulation, including as sites for lipid storage and metabolism, inflammatory lipid mediator production, and signaling pathway compartmentalization. Accumulating evidence indicates that intracellular pathogens may exploit host LDs as source of nutrients and as part of their strategy to promote immune evasion. Notably, numerous studies have demonstrated the interaction between LDs and pathogen-containing phagosomes. However, the mechanism involved in this phenomenon remains elusive. Here, we observed LDs and PLIN2 surrounding M. bovis BCG-containing phagosomes, which included observations of a bacillus cell surrounded by lipid content inside a phagosome and LAM from mycobacteria co-localizing with LDs; these results were suggestive of exchange of contents between these compartments. By using beads coated with M.tb lipids, we demonstrated that LD-phagosome associations are regulated through the mycobacterial cell wall components LAM and PIM. In addition, we demonstrated that Rab7 and RILP, but not Rab5, localizes to LDs of infected macrophages and observed the presence of Rab7 at the site of interaction with an infected phagosome. Moreover, treatment of macrophages with the Rab7 inhibitor CID1067700 significantly inhibited the association between LDs and LAM-coated beads. Altogether, our data demonstrate that LD-phagosome interactions are controlled by mycobacterial cell wall components and Rab7, which enables the exchange of contents between LDs and phagosomes and may represent a fundamental aspect of bacterial pathogenesis and immune evasion. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
