Abstract
Disease is a complex outcome that can occur as a result of pathogen-mediated damage, host-mediated damage or both. This has led to the revolutionary concept of the damage response framework (DRF) that defines microbial virulence as a function of host immunity. The DRF outlines six scenarios (classes) of host damage or beneficial outcomes, depending on the microbe and the strength of the immune response. Candida albicans is uniquely adapted to its human host and can exist as either a commensal, colonizing various anatomical sites without causing notable damage, or as a pathogen, with the ability to cause a diverse array of diseases, ranging from mucosal to invasive systemic infections that result in varying levels of microbe-mediated and/or host-mediated damage. We recently categorized six different forms of candidiasis (oropharyngeal, hematogenous, intra-abdominal, gastrointestinal, denture stomatitis, and vulvovaginitis) into independent DRF classes, supporting a contemporary view of unique mechanisms of pathogenesis for these Candida infections. In this review, we summarize the evidence for the pathogenesis of these various forms of candidiasis in the context of the DRF with the further intent to provide insights into strategies to achieve a level of host response or outcome otherwise, that limits host damage.
Highlights
The nature and extent of host damage by an opportunistic microbe were considered highly dependent on virulence attributes of the microbe
As we describe Candida infections reflecting each of the six classes of the damage response framework (DRF), we provide current and/or prospective strategies to achieve a level of host response that reduces host damage
Class 1 (OPC) and Class 2 are clearly reflective of typical ‘pathogenesis’, with the majority of damage occurring in the absence of strong host responses
Summary
The nature and extent of host damage by an opportunistic microbe were considered highly dependent on virulence attributes of the microbe. In many interactions between pathogens and normal hosts, there is a continuum between pathogen-mediated and host-mediated damage, which results in disease only when the nature of the damage impairs the normal function of the host This has led to the concept of the damage response framework (DRF) [1], which defines microbial pathogenesis as a function of the outcome of an interaction between a host and a microbe. The versatility of C. albicans, with its commensal presence and pathogenic potential at various anatomical sites, positions it in a unique situation to fit within each of the DRF classes [1,6] that collectively define Candida pathogenesis. Key terms/abbreviations used throughout the review are defined in backmatter
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