Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy.
Nerve damage is a clinical hallmark of leprosy and a major source of patient morbidity. We investigated the possibility that human Schwann cells are susceptible to cell death through the activation of Toll-like receptor 2 (TLR2), a pattern recognition receptor of the innate immune system. TLR2 was detected on the surface of human Schwann cell line ST88-14 and on cultured primary human Schwann cells. Activation of the human Schwann cell line and primary human Schwann cell cultures with a TLR2 agonist, a synthetic lipopeptide comprising the N-terminal portion of the putative Mycobacterium leprae 19-kDa lipoprotein, triggered an increase in the number of apoptotic cells. The lipopeptide-induced apoptosis of Schwann cells could be blocked by an anti-TLR2 monoclonal antibody. Schwann cells in skin lesions from leprosy patients were found to express TLR2. It was possible to identify in the lesions Schwann cells that had undergone apoptosis in vivo. The ability of M. leprae ligands to induce the apoptosis of Schwann cells through TLR2 provides a mechanism by which activation of the innate immune response contributes to nerve injury in leprosy.
Oliveira
Rosane B
RB
Division of Dermatology, Department of Microbiology and Immunology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Ochoa
Maria T
MT
Sieling
Peter A
PA
Rea
Thomas H
TH
Rambukkana
Anura
A
Sarno
Euzenir N
EN
Modlin
Robert L
RL
D017209:Apoptosis; D002478:Cells, Cultured; D004249:DNA Damage; D029721:Drosophila Proteins; D006801:Humans; D007113:Immunity, Innate; D007918:Leprosy / Q000276:immunology / Q000473:pathology*; D008074:Lipoproteins / Q000502:physiology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D012583:Schwann Cells / Q000473:pathology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors