Serologic Response to Cell Wall Mannoproteins and Proteins of Candida albicans
JOSE´ P. MARTI´NEZ, M. LUISA GIL, JOSE´ L. LO´ PEZ-RIBOT, AND W. LAJEAN CHAFFIN


INTRODUCTION.......................................................................................................................................................121
C. ALBICANS CELL WALL ......................................................................................................................................122
Composition, Structure, and Functions...............................................................................................................122
Variability and Dynamics of Cell Wall Antigens................................................................................................123
CARBOHYDRATE COMPONENT..........................................................................................................................124
Mannan ....................................................................................................................................................................124
Nonmannan Carbohydrates...................................................................................................................................127
PROTEIN COMPONENT.........................................................................................................................................127
Secreted Proteins ....................................................................................................................................................127
Secreted aspartyl proteinase .............................................................................................................................128
Immunosuppressive and B-cell mitogenic protein .........................................................................................128
Heat Shock Proteins...............................................................................................................................................128
hsp90.....................................................................................................................................................................129
hsp70.....................................................................................................................................................................129
Other heat shock proteins .................................................................................................................................129
Glycolytic Enzymes .................................................................................................................................................129
Enolase .................................................................................................................................................................130
Other glycolytic enzymes....................................................................................................................................131
Receptors and Binding Proteins for Host Ligands............................................................................................132
ANTIBODIES TO CELL WALL ANTIGENS: PROTECTIVE AND DIAGNOSTIC VALUE..........................132
SUMMARY AND OUTLOOK...................................................................................................................................134
ACKNOWLEDGMENTS ...........................................................................................................................................135
REFERENCES ............................................................................................................................................................135

SUMMARY AND OUTLOOK
Morbidity and mortality rates associated with systemic infections by C. albicans remain unacceptably high, the main reasons being the difficulties in the diagnosis and treatment of this type of infection. Many research laboratories have examined the utility of detecting antigenemia with candidal moieties or host antibodies produced to fungal antigens for diagnosis of disseminated candidiasis, and studies towards this objective continue in several laboratories (127, 253, 305). However, although urgently needed, an early, accurate, and reliable serology-based procedure for diagnosis is not commercially available and in general use, nor are alternative approaches for the therapy and prophylaxis of candidiasis available. Clearly, the development of these innovative tools can directly benefit from a better understanding of the mechanisms of pathogenicity displayed by C. albicans, especially the role of the antibody response during disseminated candidiasis. As stated above, cell wall proteins and mannoproteins of C. albicans are major elicitors of the host immune response, and our increasing knowledge of the identity and expression of these components may assist in the development of innovative tools leading to a better management of candidiasis. The demonstration of protective antibody effects has benefited from major advances in different fields such as (i) our increasing knowledge of the pathogenicity mechanisms associated with Candida infections, which can help identify opportunities for immunointervention; (ii) the identification and characterization of individual cell wall moieties displaying antigenic properties, which may represent potential candidates for vaccine development; and (iii) the advent of the monoclonal antibody and antibody engineering technologies, which have renewed interest in serum therapy as a safe, inexpensive alternative to treat infections. As stated by Matthews and Burnie (189), a number of questions need to be answered when assessing the therapeutic potential of antibodies to candidal antigens (e.g., which types of candidal infections and groups of patients would respond to antibodies, which Candida species are potentially treatable with which antibodies, and whether there is synergism between antibodies to different antigens and between antibodies and antifungal agents). However, it is expected that the currently expanding knowledge in these areas could ultimately result in the design of innovative prophylactic and therapeutic strategies for these infections.

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