Immunomodulation in response to Candida

Candidiasis may either precede or follow severe modulations in the immune system of the host. The focus of this review has been to survey the data and current interpretations for potential factors responsible for these events of immunomodulation. The mere fact that Candida infections persist is evidence of some underlying abnormality, often associated with, but not exclusively restricted to, the cell-mediated immune system. In some instances, however, the cause and effect relationship is not clear, i.e., did infection with Candida initiate the immunosuppression, or did the underlying condition result in immunosuppression allowing for Candida to initiate disease? It is possible, however, that candidal infections may begin during minor immunosuppressive events, e.g., stress, pregnancy, or selected other primary infections, but then persist beyond these events because of an intrinsic or innate immunomodulatory defect. Under such circumstances, the initial imbalance of immune function should be corrected by normal homeostatic mechanisms, unless persistent colonization with Candida perpetuates the imbalance through the production or release of immunomodulatory factors. One important target for research in this area, then, is the identification and purification of immunomodulatory factors produced or released during disease. To date, only preliminary data are available showing that the immunoregulatory potential of Candida resides in various candidal extracts, especially in the cell wall. Although the relevance of the data gathered in the experimental models might initially appear questionable, the fact that mannan, or molecules containing mannan, are known to circulate during disease (Weiner and Yount, 1976; Kerkering et al., 1979; Lehmann and Reiss, 1980) lends credence to the hypothesis. A second important target for future research is the identification of the cellular target within the immune system that responds to the Candida-derived immunomodulators. The success of these studies may well depend upon the degree of purification of the responsible factors. In fact, much of the variability observed to date in modulatory events may result from the heterogeneity of the modulator, including the possibility that antagonistic or synergistic interactions of the individual components occur. The variability observed in certain clinical settings could result from basic flaws in the normal immunoregulatory pathways in the host also, and if a link could be established between the basic flaws, the candidal extracts, and the target cell of the candidal extracts, it may be possible to manipulate the system through immunotherapy. Finally, the characterization of the candidal substances may provide yet another clinical tool for use as an immunomodulator in such disorders as cancer, inheritable immunodeficiencies, and AIDS.