Candidemia of C. Glabrata Clinical Trial
Official title:
Study of Innate Host Immune Response to C. Glabrata Clinical Isolates Resistant to Echinocandins: Impact on the Management of Candidemia in High-risk Patients
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.
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