Antigen uptake receptor for candida albicans on dendritic cells

Abstract

Dendritic cells (DC) that express the type II C-type lectin DC-SIGN (CD209) are located in the submucosa of tissues, where they mediate HIV-1 entry. Interestingly, the pathogen Candida albicans , the major cause of hospital-acquired fungal infections, is found at similar sites. Here it is demonstrated that DC-SIGN is able to bind Candida albicans both in DC-SIGN transfected cell lines and in human monocyte derived DC. Moreover, in immature DC, DC-SIGN is able to internalize Candida in specific DC-SIGN enriched vesicles, distinct from those containing the mannose receptor (MR; CD206), which is another Candida receptor on DC. Together, these results demonstrate that C. albicans has two major receptors on human monocyte derived DC, these receptors being DC-SIGN and MR. Targeting of DC-SIGN offers novel opportunities to combat chronic forms of candidiasis.

1 . A method for promoting an immune response in a subject exposed to a microorganism that binds to DC-SIGN, said method comprising administering an antigen found in said microorganism in an amount effective to bind to DC-SIGN and cause an immune response to the antigen. 
     
     
         2 . The method of  claim 1  wherein said antigen is a purified antigen. 
     
     
         3 . The method of  claim 1  wherein said antigen is an inactivated form of the microorganism. 
     
     
         4 . The method of  claim 1  wherein said antigen is bound to an antibody that binds to DC-SIGN. 
     
     
         5 . The method of  claim 1  wherein said antigen is bound to FHENWPS (SEQ ID NO: 1), β-1,2-oligomannoside, ICAM-2 or ICAM-3. 
     
     
         6 . The method of  claim 4  wherein said antibody is the antibody produced by the hybridoma cell line deposited as ECACC accession number 99040818, the antibody produced by the hybridoma cell line deposited as ECACC accession number 99040819, or the antibody produced by the hybridoma cell line deposited as ECACC accession number 03071801. 
     
     
         7 . The method of  claim 1  wherein said microorganism is a fungus. 
     
     
         8 . The method of  claim 1  wherein said microorganism is a yeast. 
     
     
         9 . The method of  claim 1  wherein said microorganism is  Candida.    
     
     
         10 . The method of  claim 9  wherein said microorganism is the species  Candida albicans, Candida dubliniensis  or  Candida glabrata.    
     
     
         11 . The method of  claim 1  wherein said microorganism is  Aspergillus fumigatus.    
     
     
         12 . The method of  claim 1  wherein said subject is a human. 
     
     
         13 . The method of  claim 1  wherein said antigen is β-1,2-oligomannoside or FHENWPS (SEQ ID NO: 1).