Candida albicans Pathogenesis: Fitting within the Host-Microbe Damage Response Framework

Abstract

f 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.

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

“…The strategies that we used to come to these conclusions (longitudinal imaging and neutrophil modulation) have not yet been applied to this question and therefore add weight to the hypothesis that neutrophil recruitment and/or activation at the site of infection controls the progression of disease. This is consistent with several studies of murine oral candidiasis but is in contrast to the findings of studies of vulvovaginal candidiasis that suggested that neutrophil recruitment is detrimental rather than protective (4). Our data also show that blockade of neutrophil recruitment results in an increased pathogen load and less damage to fungal hyphae, suggesting that neutrophils protect by damaging fungi rather than promoting disease tolerance (56).…”

“…The opportunistic nature of C. albicans mucosal infection suggests that there is a constantly challenged impasse between our immune defenses and C. albicans virulence factors (3,4). Chronic mucocutaneous candidiasis (CMC) is associated with inborn errors of adaptive immune pathways, especially Th17 immunity (5).…”

“…Neutrophils attack both the yeast and filamentous forms of C. albicans and are associated with vulvovaginal candidiasis (13)(14)(15). Counterintuitively, because symptomatic infection is more closely associated with high neutrophil numbers than with the fungal burden, it is believed that neutrophils do more to cause infection symptoms than prevent disease in the vaginal cavity (4,15,16). These contrasting activities in different tissues demonstrate that the actions of neutrophils at the site of infection can be vital for defense but must nevertheless be kept under tight control.…”

Candidalysin Drives Epithelial Signaling, Neutrophil Recruitment, and Immunopathology at the Vaginal Mucosa

“…The interplay of colonization, host response, and damage was elegantly summarized by Casadevall and Pirofski in the "damage-response framework" (DRF), a rubric describing a pathogen's ability to cause disease on a continuum of host immune status and damage capacity (38). Recently, Jabra-Rizk and colleagues revisited the DRF in the context of C. albicans pathogenesis specifically, concluding that VVC fits into class 6 of the DRF, in which a pathogen causes damage only in the context of an aggressive immune response (39). Based on these and previous findings, this appears to hold true, given that robust PMN and cytokine levels are strongly associated with disease symptomatology and centrally dependent on the capacity of Candidalysin to cause damage.…”

Comparative Evaluation of in Vitro Virulence of Mould Isolates from Clinical Cases and from Air Samples and Their Mortality Rates in Galleria mellonella Larvae

“…Havadan izole edilen bir Aspergillus kökeni ile enfeksiyon etkeni olan bir başka Aspergillus kökeni arasın-daki virülans farkının araştırıldığı az sayıda yayın bulunmaktadır (1) . Mantarların virülans faktörleri genellikle maya mantarları ve en çok da Candida cinsi ile çalışılmıştır (5) . Hayvan modelleri ile yapılan in vivo çalışma sayısı ise daha da azdır (6) .…”