Cell Wall Constituents of Candida Albicans as Biological Response Modifiers

Abstract

Candida albicans is an opportunistic fungal agent which has become a highly prevalent and incident cause of disease, especially life-threatening in neutropenic, bone-marrow transplanted subjects with underlying malignant hemopathy^1,2. An extensive experimental evidence demonstrates that this fungus, and materials extracted from it, can also be used to influence or modify multiple biologic functions^3,4. A particular point of interest in the “Biological Response Modifier” (BRM)-activities of Candida, that make this microorganism quite particular in comparison to other more popular microbial immunomodulators (for instance, BCG), is that Candida is a human commensal. Thus, almost every normal subject is primed for immune response to candidal antigens, as shown by the presence in its serum of measurable, sometimes elevated, levels of specific antibodies, and positive cell-mediated response to Candida antigens ^5,6. While generating restrictions to the use of certain fungal materials as immunomodulators (mostly concerning undesired hypersensitivity reactions) the human commensalism also tells us that Candida-induced immunomodulation may take place under natural conditions and can be easily amplified. A rather dramatic example of this amplification is the generation of LAK- like effectors following Candida vaccination of normal mice⁷ or exposure of peripheral blood mononuclear cells (PBMC) from normal human donors to a mannoprotein extract of C. albicans ⁸. Moreover, certain fungal products are potent recall antigens to probe the efficiency of the immune system, both in normal and pathological conditions^9,10 Most of the BRM-effects of C. albicans are mediated by the glucan and the mannoprotein constituents of the fungal cell wall⁴. In this note, we will mostly address the latter components (hereafter referred to as MP), and will attempt to summarize some of our recent results on the immunogenic and immunomodulatory effects of a purified and chemically-characterized mannoprotein fraction (F2).