Involvement of 9-O-Acetyl GD3 ganglioside in Mycobacterium leprae infection of Schwann cells.
Mycobacterium leprae (ML), the etiologic agent of leprosy, mainly affects the skin and peripheral nerves, leading to demyelization and loss of axonal conductance. Schwann cells (SCs) are the main cell population infected by ML in the nerves, and infection triggers changes in the SC phenotype from a myelinated to a nonmyelinated state. In the present study, we show that expression of 9-O-acetyl GD3, a ganglioside involved in cellular anti-apoptotic signaling and nerve regeneration, increases in SCs following infection with ML. Observation by confocal microscopy together with coimmunoprecipitation suggested that this ganglioside participates in ML attachment and internalization by SC. Immunoblockage of 9-O-acetyl GD3 in vitro significantly reduced adhesion of ML to SC surfaces. Finally, we show that activation of the MAPK (ERK 1/2) pathway and SC proliferation, two known effects of ML on SCs that result in demyelization, are significantly reduced when the 9-O-acetyl GD3 ganglioside is immunoblocked. Taken together, these data suggest the involvement of 9-O-acetyl GD3 in ML infection on SCs.
Ribeiro-Resende
Victor Túlio
VT
Laboratório de Microbiologia Celular, Pavilhão de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21045-900 Rio de Janeiro, Brazil and.
Ribeiro-Guimarães
Michelle Lopes
ML
Lemes
Robertha Mariana Rodrigues
RM
Nascimento
Isis Cristina
IC
Alves
Lucinéia
L
Mendez-Otero
Rosalia
R
Pessolani
Maria Cristina Vidal
MC
Lara
Flávio Alves
FA
D000818:Animals; D017209:Apoptosis; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007918:Leprosy / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009166:Mycobacterium leprae / Q000378:metabolism*; D009186:Myelin Sheath / Q000737:chemistry; D009474:Neurons / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000382:microbiology*; D015398:Signal Transduction
D005732:Gangliosides; D019012:Integrin beta1; C049132:9-O-acetyl-GD3 ganglioside