IMMUNOGENIC AND IMMUNOMODULATORY PROPERTIES OF MANNOPROTEINS FROM CANDIDA-ALBICANS

Authors
Citation
A. Cassone, IMMUNOGENIC AND IMMUNOMODULATORY PROPERTIES OF MANNOPROTEINS FROM CANDIDA-ALBICANS, Canadian journal of botany, 73, 1995, pp. 1192-1198
Citations number
36
Journal title
ISSN journal
00084026
Volume
73
Year of publication
1995
Supplement
1
Pages
1192 - 1198
Database
ISI
SICI code
0008-4026(1995)73:<1192:IAIPOM>2.0.ZU;2-8
Abstract
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.