Domer J E, Garner R E
Tulane University School of Medicine, New Orleans, Louisiana.
Immunol Ser. 1989;47:293-317.
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.
念珠菌病可能先于或继发于宿主免疫系统的严重调节异常。本综述的重点是调查有关导致这些免疫调节事件的潜在因素的数据及当前的解释。念珠菌感染持续存在这一事实本身就证明存在某些潜在异常，这些异常通常与细胞介导的免疫系统有关，但并非仅局限于此。然而，在某些情况下，因果关系并不明确，即念珠菌感染是引发了免疫抑制，还是潜在疾病导致了免疫抑制从而使念珠菌引发疾病？不过，念珠菌感染有可能在轻微免疫抑制事件（如应激、妊娠或某些其他原发性感染）期间开始，但随后由于内在或先天性免疫调节缺陷而在这些事件之后持续存在。在这种情况下，免疫功能的初始失衡应通过正常的稳态机制得到纠正，除非念珠菌的持续定植通过免疫调节因子的产生或释放使失衡持续存在。那么，该领域研究的一个重要目标就是鉴定和纯化疾病期间产生或释放的免疫调节因子。迄今为止，仅有初步数据表明念珠菌的免疫调节潜能存在于各种念珠菌提取物中，尤其是细胞壁中。尽管在实验模型中收集的数据相关性最初可能看似存疑，但甘露聚糖或含甘露聚糖的分子在疾病期间会循环这一事实（韦纳和扬特，1976年；克尔克林等人，1979年；莱曼和赖斯，1980年）为该假说提供了可信度。未来研究的第二个重要目标是确定免疫系统内对念珠菌衍生的免疫调节剂作出反应的细胞靶点。这些研究的成功很可能取决于相关因子的纯化程度。事实上，迄今为止在调节事件中观察到的许多变异性可能是由于调节剂的异质性，包括各个成分之间可能发生拮抗或协同相互作用的可能性。在某些临床环境中观察到的变异性也可能是由于宿主正常免疫调节途径中的基本缺陷，如果能在这些基本缺陷、念珠菌提取物和念珠菌提取物的靶细胞之间建立联系，就有可能通过免疫疗法来操控该系统。最后，念珠菌物质的特性描述可能会提供另一种临床工具，用作癌症、遗传性免疫缺陷和艾滋病等疾病的免疫调节剂。
