Epitope unmasking in vulvovaginal candidiasis is associated with hyphal growth and neutrophilic infiltration

Abstract

Vaginal candidiasis is a common disorder in women of childbearing age, caused primarily by the dimorphic fungus Candida albicans. Since C. albicans is a normal commensal of the vaginal mucosa, a long-standing question is how the fungus switches from being a harmless commensal to a virulent pathogen. Work with human subjects and in mouse disease models suggests that host inflammatory processes drive the onset of symptomatic infection. Fungal cell wall molecules can induce inflammation through activation of epithelial and immune receptors that trigger pro-inflammatory cytokines and chemokines, but pathogenic fungi can evade recognition by masking these molecules. Knowledge about which cell wall epitopes are available for immune recognition during human infection could implicate specific ligands and receptors in the symptoms of vaginal candidiasis. To address this important gap, we directly probed the surface of fungi present in fresh vaginal samples obtained both from women with symptomatic Candida vaginitis and from women that are colonized but asymptomatic. We find that the pro-inflammatory cell wall polysaccharide β-glucan is largely masked from immune recognition, especially on yeast. It is only exposed on a small percentage of hyphal cells, where it tends to co-localize with enhanced levels of chitin. Enhanced β-glucan availability is only found in symptomatic patients with strong neutrophil infiltration, implicating neutrophils as a possible driver of these cell wall changes. This is especially interesting because neutrophils were recently shown to be necessary and sufficient to provoke enhanced β-glucan exposure in C. albicans, accompanied by elevated immune responses. Taken together, our data suggest that the architecture of C. albicans cell wall can be altered by environmental stress during vaginal candidiasis.

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

“…According to Ahn et al, LTA from L. plantarum K8 also modulated inflammatory cytokines (TNF-α and IL-10) production in LPS-challenged THP-1 cells [ 205 ]. Patients with BV, sexually-transmitted diseases are often associated with overstimulation of pro-inflammatory cytokines and neutrophils recruitment to vagina mucosa surface [ 119 , 206 ]. Thus, the immunomodulatory activity of lactobacilli LTA could dampen the overstimulation and vaginal inflammation caused by pathogens.…”

On‐site secretory vesicle delivery drives filamentous growth in the fungal pathogenCandida albicans

“…Candida albicans is a human fungal pathogen that switches between an oval yeast form and a filamentous hyphal form, a transition which is critical for virulence (Moyes, Richardson, & Naglik, 2015). This morphological transition is accompanied, in particular, by changes in the cell wall that are critical for host immune responses (Gow & Hube, 2012;Hall & Gow, 2013;Lewis et al, 2012;Pericolini et al, 2018;Wheeler, Kombe, Agarwala, & Fink, 2008). In susceptible hosts, C. albicans can penetrate the gastrointestinal mucosa and enter the bloodstream leading to severe systemic infection (Pfaller & Diekema, 2010).…”

Oestrogen promotes innate immune evasion ofCandida albicansthrough inactivation of the alternative complement system

“…The interaction between C. albicans and innate immune cells can be mediated via direct detection of fungal cell wall carbohydrates and opsin mediated phagocytosis (opsonophagocytosis). Adaptation of C. albicans to a variety of environmental conditions influences the Candida host-pathogen interaction, through altered Dectin-1 dependent recognition of β-glucan, which correlates with altered pro-inflammatory cytokine secretion (Wheeler and Fink 2006, Wheeler et al 2008, Hall 2015, Ballou et al 2016, Hopke et al 2016, Sherrington et al 2017, Lopes et al 2018, Pericolini et al 2018, Pradhan et al 2018, Pradhan et al 2019, Tripathi et al 2020, Williams and Lorenz 2020. However, oestrogen did not affect the amount or exposure of the main cell wall carbohydrates ( Fig S2A-E), and did not significantly impact on the section of pro-inflammatory cytokines (Fig S2F-I).…”

“…In addition, many components of the cell wall act as pathogen associated molecular patterns (PAMPs) and are recognised by the innate immune system (Netea et al 2008, Hall andGow 2013). Recently, remodelling of the cell wall in response to adaptation to host environments has been shown to regulate the host-pathogen interaction (Wheeler and Fink 2006, Wheeler et al 2008, Hall 2015, Ballou et al 2016, Hopke et al 2016, Sherrington et al 2017, Lopes et al 2018, Pericolini et al 2018, Pradhan et al 2018, Pradhan et al 2019, Tripathi et al 2020, Williams and Lorenz 2020. In addition to direct recognition of cell wall PAMPs mediating phagocytosis, C. albicans also activates the alternative complement system, resulting in the deposition of complement proteins (i.e.…”