Functional comparison of the mouse DC‐SIGN, SIGNR1, SIGNR3 and Langerin, C‐type lectins

The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these lectins—DC-SIGN, SIGNR1 and SIGNR3—to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC‐dextran, FITC‐ovalbumin, zymosan or heat-killed Candida albicans. The other three lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC‐dextran uptake at 37∞C and by mannan binding activity at 4∞C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gramnegative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC‐zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b + cells expressing SIGNR1 bound zymosan at 4∞C in concert with a laminarinsensitive receptor. Therefore these homologous C-type lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.