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.
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
E J
EJ
Soilleux
E N
EN
Sarno
M O
MO
Hernandez
E
E
Moseley
J
J
Horsley
U G
UG
Lopes
M J
MJ
Goddard
S L
SL
Vowler
N
N
Coleman
R J
RJ
Shattock
E P
EP
Sampaio
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