DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?
The clinical spectrum of leprosy is related to patients' immune responses. Non-responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2 cytokine profile. The reason for such a polarized immune response remains unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells (DCs) and macrophages, has previously been associated with Th2 responses. Here we show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis, through the cell wall component lipoarabinomannan. DC-SIGN is expressed on virtually all ML-containing cells, providing further evidence for its role as a receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy and may then contribute to mycobacterial entry into these cells.
Soilleux
E J
EJ
Department of Histopathology, Papworth Hospital, Papworth Everard, Cambridge CB3 8RE, and Nuffield Department of Clinical Laboratory Sciences, University of Oxford, UK. E.J.Soilleux.91@cantab.net
Sarno
E N
EN
Hernandez
M O
MO
Moseley
E
E
Horsley
J
J
Lopes
U G
UG
Goddard
M J
MJ
Vowler
S L
SL
Coleman
N
N
Shattock
R J
RJ
Sampaio
E P
EP
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D003470:Culture Media; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D007918:Leprosy / Q000276:immunology*; D015439:Leprosy, Borderline / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014162:Transfection / Q000379:methods; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000942:Antigens, Bacterial; D015815:Cell Adhesion Molecules; D003470:Culture Media; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C050016:lipoarabinomannan