Rab7 controls lipid droplet-phagosome association during mycobacterial infection.

Autor: Roque NR; Laboratório de Imunofarmacologia, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil., Lage SL; Laboratório de Imunofarmacologia, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil., Navarro R; Laboratório de Imunofarmacologia, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil., Fazolini N; Laboratório de Imunofarmacologia, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil., Maya-Monteiro CM; Laboratório de Imunofarmacologia, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil., Rietdorf J; Centro de Desenvolvimento Tecnológico em Saúde, CDTS, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil., Melo RCN; Laboratório de Biologia Celular, Departamento de Biologia, Universidade Federal de Juiz de Fora, Juiz de Fora, 36036-330, MG, Brazil., D'Avila H; Laboratório de Biologia Celular, Departamento de Biologia, Universidade Federal de Juiz de Fora, Juiz de Fora, 36036-330, MG, Brazil., Bozza PT; Laboratório de Imunofarmacologia, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, 21045-900, RJ, Brazil. Electronic address: pbozza@ioc.fiocruz.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2020 Aug; Vol. 1865 (8), pp. 158703. Date of Electronic Publication: 2020 Mar 27.
DOI: 10.1016/j.bbalip.2020.158703
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2020. Published by Elsevier B.V.)
Databáze: MEDLINE
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