Candida albicans is a human commensal and opportunistic fungal organis
m 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 in
stance, we have recently found that a protein moiety of a 65-kDa manno
protein is a major target of cell-mediated immune response. The patter
n of cytokines produced by mannoprotein-stimulated human mononuclear c
ell cultures and mannoprotein-specific T cell lines demonstrated abund
ant interferon-gamma 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 cyto
kine pattern was seen in splenocyte cultures of mice chronically infec
ted with a low-virulence Candida strain (CA-2) and then stimulated in
vitro with MP-65-containing mannoprotein fractions, or also in mice im
munized with these fractions. On the other hand, the mannan moieties o
f mannoproteins bear major B cell epitopes that are responsible for se
rological specificity, acid the ordinary antibody response mounted dur
ing normal host colonization. Indirect evidence for the importance of
this response for the host- Candida relationship is the dramatic modul
ation of mannan epitopes on the cell surface during growth and morphol
ogical development in vivo. One such epitope is a phosphorylated beta-
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 polymorphonuclea
r cells and release of a variety of pro-inflammatory and immunomodulat
ory cytokines, in particular interleukin-1 beta and tumor necrosis fac
tor-alpha. Overall, these studies emphasize the need for further defin
ition of individual mannoprotein constituents to dissect the multiple
biological actions of these highly complex, multifunctional molecular
within C. albicans.