Translational Research in Respiratory Diseases Program, Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Division of Experimental Medicine, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.
Front Immunol. 2019 Jan 29;10:66. doi: 10.3389/fimmu.2019.00066. eCollection 2019.
is a ubiquitous environmental yeast and a leading cause of invasive fungal infection in humans. The most recent estimate of global disease burden includes over 200,000 cases of cryptococcal meningitis each year. expresses several virulence factors that may have originally evolved to protect against environmental threats, and human infection may be an unintended consequence of these acquired defenses. Traditionally, has been viewed as a purely opportunistic pathogen that targets severely immune compromised hosts; however, during the past decade the spectrum of susceptible individuals has grown considerably. In addition, the closely related strain has recently emerged in North America and preferentially targets individuals with intact immunity. In parallel to the changing epidemiology of cryptococcosis, an increasing role for host immunity in the pathogenesis of severe disease has been elucidated. Initially, the HIV/AIDS epidemic revealed the capacity of to cause host damage in the absence of adaptive immunity. Subsequently, the development and clinical implementation of highly active antiretroviral treatment (HAART) led to recognition of an immune reconstitution inflammatory syndrome (IRIS) in a subset of HIV+ individuals, demonstrating the pathological role of host immunity in disease. A post-infectious inflammatory syndrome (PIIRS) characterized by abnormal T cell-macrophage activation has also been documented in HIV-negative individuals following antifungal therapy. These novel clinical conditions illustrate the highly complex host-pathogen relationship that underlies severe cryptococcal disease and the intricate balance between tolerance and resistance that is necessary for effective resolution. In this article, we will review current knowledge of the interactions between cryptococci and mammalian hosts that result in a tolerant phenotype. Future investigations in this area have potential for translation into improved therapies for affected individuals.
是一种普遍存在的环境酵母，也是人类侵袭性真菌感染的主要原因。最近对全球疾病负担的估计包括每年超过 200,000 例隐球菌性脑膜炎病例。表达了几种毒力因子，这些毒力因子可能最初是为了抵御环境威胁而进化的，而人类感染可能是这些获得性防御的意外后果。传统上，被认为是一种纯粹的机会性病原体，针对严重免疫受损的宿主；然而，在过去的十年中，易感个体的范围大大扩大。此外，最近在北美的密切相关菌株已出现，并优先针对具有完整免疫的个体。与隐球菌病的流行病学变化并行的是，宿主免疫在严重疾病发病机制中的作用日益增加。最初，艾滋病毒/艾滋病流行揭示了在没有适应性免疫的情况下，能够导致宿主损伤。随后，高效抗逆转录病毒治疗（HAART）的发展和临床实施导致人们认识到 HIV+个体中的一部分存在免疫重建炎症综合征（IRIS），这表明宿主免疫在疾病中的病理作用。在接受抗真菌治疗后，HIV 阴性个体也记录了一种称为感染后炎症综合征（PIIRS）的异常 T 细胞-巨噬细胞激活。这些新的临床情况说明了严重隐球菌病背后的高度复杂的宿主-病原体关系，以及为了有效解决问题而必需的耐受和抵抗之间的复杂平衡。在本文中，我们将回顾目前关于隐球菌和哺乳动物宿主之间相互作用的知识，这些相互作用导致了耐受表型。该领域的未来研究有可能转化为改善受影响个体的治疗方法。
