Jabra-Rizk Mary Ann, Kong Eric F, Tsui Christina, Nguyen M Hong, Clancy Cornelius J, Fidel Paul L, Noverr Mairi
Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA
Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, Maryland, USA Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, USA Graduate Program in Life Sciences, Molecular Microbiology and Immunology Program, University of Maryland, Baltimore, Maryland, USA.
Infect Immun. 2016 Sep 19;84(10):2724-39. doi: 10.1128/IAI.00469-16. Print 2016 Oct.
Historically, the nature and extent of host damage by a microbe were considered highly dependent on virulence attributes of the microbe. However, it has become clear that disease is a complex outcome which can arise because of pathogen-mediated damage, host-mediated damage, or both, with active participation from the host microbiota. This awareness led to the formulation of the damage response framework (DRF), a revolutionary concept that defined microbial virulence as a function of host immunity. The DRF outlines six classifications of host damage outcomes based on the microbe and the strength of the immune response. In this review, we revisit this concept from the perspective of Candida albicans, a microbial pathogen uniquely adapted to its human host. This fungus commonly colonizes various anatomical sites without causing notable damage. However, depending on environmental conditions, a diverse array of diseases may occur, ranging from mucosal to invasive systemic infections resulting in microbe-mediated and/or host-mediated damage. Remarkably, C. albicans infections can fit into all six DRF classifications, depending on the anatomical site and associated host immune response. Here, we highlight some of these diverse and site-specific diseases and how they fit the DRF classifications, and we describe the animal models available to uncover pathogenic mechanisms and related host immune responses.
从历史上看，微生物对宿主造成损害的性质和程度被认为高度依赖于微生物的毒力属性。然而，现在已经清楚的是，疾病是一种复杂的结果，它可能是由于病原体介导的损害、宿主介导的损害或两者兼而有之，并在宿主微生物群的积极参与下产生的。这种认识导致了损伤反应框架（DRF）的形成，这是一个革命性的概念，将微生物毒力定义为宿主免疫力的函数。DRF根据微生物和免疫反应的强度概述了宿主损伤结果的六种分类。在这篇综述中，我们从白色念珠菌的角度重新审视这个概念，白色念珠菌是一种独特地适应其人类宿主的微生物病原体。这种真菌通常在各种解剖部位定殖而不会造成明显损害。然而，根据环境条件，可能会发生各种各样的疾病，从黏膜感染到侵袭性全身感染，导致微生物介导和/或宿主介导的损害。值得注意的是，根据解剖部位和相关的宿主免疫反应，白色念珠菌感染可以符合所有六种DRF分类。在这里，我们重点介绍其中一些多样的、特定部位的疾病以及它们如何符合DRF分类，并描述可用于揭示致病机制和相关宿主免疫反应的动物模型。
