Immunogenic and immunomodulatory properties of mannoproteins from Candida albicans

Abstract

Candida albicans is a human commensal and opportunistic fungal organism that expresses on its surface and releases into the external milieu a variety of mannoprotein molecules that are relevant in many aspects of host–Candida relationship. We have attempted to relate mannoprotein constituents to the microbial function and (or) host response. For instance, we have recently found that a protein moiety of a 65-kDa mannoprotein is a major target of cell-mediated immune response. The pattern of cytokines produced by mannoprotein-stimulated human mononuclear cell cultures and mannoprotein-specific T cell lines demonstrated abundant interferon-γ and interleukin-2 production with very low or no production of interleukin-4 and interleukin-10, which suggests that MP-65 is recognized by CD4+ cells of T helper 1 subset. A similar cytokine pattern was seen in splenocyte cultures of mice chronically infected with a low-virulence Candida strain (CA-2) and then stimulated in vitro with MP-65-containing mannoprotein fractions, or also in mice immunized with these fractions. On the other hand, the mannan moieties of mannoproteins bear major B cell epitopes that are responsible for serological specificity, and the ordinary antibody response mounted during normal host colonization. Indirect evidence for the importance of this response for the host–Candida relationship is the dramatic modulation of mannan epitopes on the cell surface during growth and morphological development in vivo. One such epitope is a phosphorylated β-1,2-oligomannoside recognized by the monoclonal antibody AF1, which is present on the surface of infecting yeast cells but then lost during an experimental vaginal infection. Finally, mannan moieties also exert powerful activation of the antimicrobial activity of polymorphonuclear cells and release of a variety of pro-inflammatory and immunomodulatory cytokines, in particular interleukin-1β and tumor necrosis factor-α. Overall, these studies emphasize the need for further definition of individual mannoprotein constituents to dissect the multiple biological actions of these highly complex, multifunctional molecular within C. albicans. Key words: mannoproteins, Candida albicans, immunogenicity, immunomodulation.