Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Catholic University of Rome, Rome, Italy.
AIDS. 2012 Jul 31;26(12):1457-72. doi: 10.1097/QAD.0b013e3283536ba8.
In this era of efficacious antiretroviral therapy and consequent immune reconstitution, oropharyngeal and esophageal candidiasis (OPC and OEC) still remain two clinically relevant presentations in the global HIV setting. Both diseases are predominantly caused by Candida albicans, a polymorphic fungus which is a commensal microbe in the healthy individual but can become an aggressive pathogen in a debilitated host. Actually, C. albicans commensalism is not the result of a benign behavior of one of the many components of human microbiota, but rather the result of host's potent innate and adaptive immune responses that restrict the growth of a potentially dangerous microrganism on the epithelia. An important asset guarding against the fungus is the Th17 functional subset of T helper cells. The selective loss of these cells with the progression of HIV infection causes the decay of fungal containment on the oral epithelium and allows C. albicans to express its pathogenic potential. An important part of this potential is represented by mechanisms to evade host immunity and enhance inflammation and immunoactivation. In C. albicans, these mechanisms are mostly incorporated into and expressed by characteristic morphogenic transitions such as the yeast-to-hyphal growth and the white-to-opaque switch. In addition, HIV infection generates an 'environment' selecting for overexpression of the virulence potential by the fungus, particularly concerning the secreted aspartyl proteinases (Saps). These enzymes can degrade critical host defense components such as complement and epithelial defensive proteins such as histatin-5 and E-cadherin. It appears that part of this enhanced Candida virulence could be induced by the binding of the fungus to HIV and/or induced by HIV proteins such as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics, but in the absence of host collaboration, anticandidal therapy may become ineffective in the long run. For these reasons, new therapeutics targeting virulence factors and specific immune interventions are being addressed. Among these new approaches, vaccination is a promising one. Two subunit vaccines based on antigens dominantly expressed by C. albicans in vivo, that is the Als3 adhesin and Sap2, have recently undergone phase 1 clinical trials. Overall, studies of Candida and candidiasis in the HIV-positive patient while certainly contributing to a more effective control of the microorganism may also provide useful information on HIV-host relationship itself that can assist the fight against the virus.
在有效的抗逆转录病毒治疗和随之而来的免疫重建时代，口腔和食管念珠菌病（OPC 和 OEC）仍然是全球 HIV 环境中的两种具有临床相关性的表现。这两种疾病主要由白色念珠菌引起，白色念珠菌是一种多态真菌，在健康个体中是共生微生物，但在虚弱宿主中可成为侵袭性病原体。实际上，白色念珠菌共生并不是人类微生物组众多成分之一的良性行为的结果，而是宿主强大的先天和适应性免疫反应的结果，这些反应限制了潜在危险微生物在表皮上的生长。保护人体免受真菌侵害的一个重要因素是 Th17 辅助性 T 细胞功能亚群。随着 HIV 感染的进展，这些细胞的选择性丧失导致口腔上皮对真菌的抑制作用减弱，使白色念珠菌能够表达其致病潜能。这种潜在能力的一个重要部分是通过逃避宿主免疫、增强炎症和免疫激活的机制来实现的。在白色念珠菌中，这些机制主要包含在特征形态发生转变中，并由其表达，如酵母到菌丝的生长和白到不透明的转变。此外，HIV 感染会产生一种“环境”，选择真菌过度表达其毒力潜能，特别是涉及到分泌的天冬氨酸蛋白酶（Saps）。这些酶可以降解关键的宿主防御成分，如补体和上皮防御蛋白，如组蛋白-5 和 E-钙粘蛋白。似乎这种增强的白色念珠菌毒力的一部分是由真菌与 HIV 的结合诱导的，或者是由 HIV 蛋白，如 gp160 和 tat 诱导的。OPC 和 OEC 都可以用旧的和新的抗真菌药物来控制，但如果没有宿主的合作，抗真菌治疗从长远来看可能会失效。出于这些原因，正在针对毒力因子和特定免疫干预措施开发新的治疗方法。在这些新方法中，疫苗是一种很有前途的方法。两种基于白色念珠菌在体内主要表达的抗原的亚单位疫苗，即 Als3 黏附素和 Sap2，最近已经进行了 1 期临床试验。总的来说，对 HIV 阳性患者中的白色念珠菌和念珠菌病的研究，虽然肯定有助于更有效地控制这种微生物，但也可以为 HIV-宿主关系本身提供有用的信息，这可以帮助对抗病毒。
