Modulation of lipid droplets by Mycobacterium leprae in Schwann cells: a putative mechanism for host lipid acquisition and bacterial survival in phagosomes.
The predilection of Mycobacterium leprae (ML) for Schwann cells (SCs) leads to peripheral neuropathy, a major concern in leprosy. Highly infected SCs in lepromatous leprosy nerves show a foamy, lipid-laden appearance; but the origin and nature of these lipids, as well as their role in leprosy, have remained unclear. The data presented show that ML has a pronounced effect on host-cell lipid homeostasis through regulation of lipid droplet (lipid bodies, LD) biogenesis and intracellular distribution. Electron microscopy and immunohistochemical analysis of lepromatous leprosy nerves for adipose differentiation-related protein expression, a classical LD marker, revealed accumulating LDs in close association to ML in infected SCs. The capacity of ML to induce LD formation was confirmed in in vitro studies with human SCs. Moreover, via confocal and live-cell analysis, it was found that LDs are promptly recruited to bacterial phagosomes and that this process depends on cytoskeletal reorganization and PI3K signalling. ML-induced LD biogenesis and recruitment were found to be independent of TLR2 bacterial sensing. Notably, LD recruitment impairment by cytoskeleton drugs decreased intracellular bacterial survival. Altogether, our data revealed SC lipid accumulation in ML-containing phagosomes, which may represent a fundamental aspect of bacterial pathogenesis in the nerve.
Mattos
Katherine A
KA
Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Lara
Flavio A
FA
Oliveira
Viviane G C
VG
Rodrigues
Luciana S
LS
D'Avila
Heloisa
H
Melo
Rossana C N
RC
Manso
Pedro P A
PP
Sarno
Euzenir N
EN
Bozza
Patricia T
PT
Pessolani
Maria Cristina V
MC
D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000032:analysis; D050296:Microbial Viability; D008853:Microscopy; D009166:Mycobacterium leprae / Q000378:metabolism / Q000472:pathogenicity*; D000070780:Perilipin-2; D010588:Phagosomes / Q000382:microbiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012583:Schwann Cells / Q000382:microbiology*; D015398:Signal Transduction
D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; D019869:Phosphatidylinositol 3-Kinases