Novel structural features in Candida albicans hyphal glucan provide a basis for differential innate immune recognition of hyphae versus yeast [Immunology]

December 16th, 2013 by Lowman, D. W., Greene, R. R., Bearden, D. W., Kruppa, M. D., Pottier, M., Monteiro, M. A., Soldatov, D. V., Ensley, H. E., Cheng, S.-C., Netea, M. G., Williams, D. L.

The innate immune system differentially recognizes Candida albicans yeast and hyphae. It is not clear how the innate immune system effectively discriminates between yeast and hyphal forms of C. albicans. Glucans are major components of the fungal cell wall and key fungal pathogen-associated molecular patterns. C. albicans yeast glucan has been characterized; however, little is known about glucan structure in C. albicans hyphae. Using an extraction procedure which minimizes degradation of the native structure, we extracted glucans from C. albicans hyphal cell walls. 1H-NMR data analysis revealed that, when compared to reference (1-3,1-6) beta-linked glucans and C. albicans yeast glucan, hyphal glucan has a unique cyclical or closed chain structure which is not found in yeast glucan. GC/MS analyses showed high abundance of 3- and 6-linked glucose units when compared to yeast beta-glucan. In addition, to the expected (1-3), (1-6) and 3,6 linkages, we also identified a 2,3 linkage which has not been reported previously in C. albicans. Hyphal glucan induced robust immune responses in human peripheral blood mononuclear cells and macrophages via a Dectin-1-dependent mechanism. In contrast, C. albicans yeast glucan was a much less potent stimulus. We also demonstrated the capacity of C. albicans hyphal glucan, but not yeast glucan, to induce IL-1beta processing and secretion. This finding provides important evidence for understanding the immune discrimination between colonization and invasion at the mucosal level. When taken together, these data provide a structural basis for differential innate immune recognition of C. albicans yeast versus hyphae.
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