Study of Innate Host Immune Response to C. Glabrata Clinical Isolates Resistant to Echinocandins: Impact on the Management of Candidemia in High-risk Patients
- Conditions
- Candidemia of C. Glabrata
- Interventions
- Other: in vitro evaluation of epithelial immune response during C. glabrata infectionOther: study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates
- Registration Number
- NCT03652194
- Lead Sponsor
- Centre Hospitalier Universitaire Dijon
- Brief Summary
In the context of Candida yeast infections, a large number of studies have been published over the past two decades specifying the molecular mechanisms of antifungal resistance in different Candida species. However, few of these studies have explored how these mechanisms influence host immune response to this opportunistic pathogen. Recent advances in understanding how the host's immune system responds to Candida have initiated the emergence of a new research theme aimed at better understanding Candida's intrinsic and adaptive resistance mechanisms to antifungals can modulate "escape to" or "recognition by" the host's immune system. This knowledge could lead to (i) a better understanding of the predominance of certain Candida species with antifungal resistance in certain patient populations, (ii) a better understanding of why high levels of in vitro resistance are not necessarily correlated with in vivo therapeutic failure, and (iii) effective immunotherapeutic strategies to control Candida resistance to antifungals.
It is therefore crucial to investigate the impact of Candida's resistance to antifungals on the host's innate immune response. Indeed, most antifungal resistance mechanisms have a direct or indirect structural modification of the fungal wall. However, it is the composition of this wall that is involved in the recognition of Candida by the host cell via the pattern recognition receptors (PRRs). We therefore put forward the very probable hypothesis that changes in the fungal wall, induced by the appearance of resistance, could alter the recognition of Candida by PRRs and thus trigger a different immune response, either qualitatively (type of cytokines secreted) or quantitatively (amplitude and duration of the immune response). However, even if initial experimental data support the hypothesis of a possible link between resistance and a modulation of the innate immune response in digestive mucosa (the most frequent starting point for disseminated candidiasis), many questions remain regarding (i) the proteins and mechanisms of the modulated immune cascade, (ii) the modification of the immune response according to the Candida species in question and (iii) the modification of the immune response according to the resistance phenotype in question.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 21
- 10 clinical isolates sensitive to all antifungal agents
- 10 echinocandin-resistant clinical isolates (Eucast, caspofungin > 8µg/ml)
Clinical strains of C. glabrata susceptible or resistant to echinocandins will be selected on selected criteria:
- patient's immune status
- therapeutic management
- clinical developments
- Not applicable
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Echinocandin-resistant clinical isolates study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates 10 echinocandin-resistant clinical isolates (Eucast, Caspofungin \> 8µg/ml) Clinical isolates sensitive to all antifungal agents in vitro evaluation of epithelial immune response during C. glabrata infection 10 clinical isolates sensitive to all Echinocandin-resistant clinical isolates in vitro evaluation of epithelial immune response during C. glabrata infection 10 echinocandin-resistant clinical isolates (Eucast, Caspofungin \> 8µg/ml) Reference strain ATCC study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates 1 strain sensitive to all antifungals Clinical isolates sensitive to all antifungal agents study of the impact of resistance phenotype acquisition on the virulence of C. glabrata isolates 10 clinical isolates sensitive to all Reference strain ATCC in vitro evaluation of epithelial immune response during C. glabrata infection 1 strain sensitive to all antifungals
- Primary Outcome Measures
Name Time Method Test SytoxOrange Baseline In vitro study of different cytotoxicity markers in digestive epithelial cells
Quantification of the gene expression of the various cytokines associated with the immune response in digestive epithelial cells. Baseline Quantification of accession and invasion Baseline In vitro study of different virulence markers
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Chu Dijon Bourogne
🇫🇷Dijon, France