Host genetic signatures of susceptibility to fungal disease

Our relative inability to predict the development of fungal disease and its clinical outcome raises fundamental questions about its actual pathogenesis. Several clinical risk factors are described to predispose to fungal disease, particularly in immunocompromised and severely ill patients. However, these alone do not entirely explain why, under comparable clinical conditions, only some patients develop infection. Recent clinical and epidemiological studies have reported an expanding number of monogenic defects and common polymorphisms associated with fungal disease. By directly implicating genetic variation in the functional regulation of immune mediators and interacting pathways, these studies have provided critical insights into the human immunobiology of fungal disease. Most of the common genetic defects reported were described or suggested to impair fungal recognition by the innate immune system. Here, we review common genetic variation in pattern recognition receptors and its impact on the immune response against the two major fungal pathogens Candida albicans and Aspergillus fumigatus. In addition, we discuss potential strategies and opportunities for the clinical translation of genetic information in the field of medical mycology. These approaches are expected to transfigure current clinical practice by unleashing an unprecedented ability to personalize prophylaxis, therapy and monitoring for fungal disease.This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to AC, and SFRH/BPD/96176/2013 to CC), the Institut Mérieux (Mérieux Research Grant 2017 to CC), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017 to AC)

Genetic basis for recurrent vulvo-vaginal candidiasis

Item does not contain fulltextVulvovaginal candidiasis (VVC) is a frequent disease affecting more than 75% of all women at least once in their lifetime. Up to 8% of them suffer from recurrent VVC (RVVC) characterized by at least three episodes each year. Several risk factors, such as antibiotic use, diabetes, or pregnancy, are known, but the vast majority of women with RVVC develop the infection without having any risk factor, implying that a genetic component most likely plays an important role in the susceptibility to RVVC. This review summarizes the immunogenetic alterations that lead to an increased susceptibility to vaginal infections with Candida albicans. Different mutations and polymorphisms in innate immune genes alter the mucosal immune response against fungi and are likely to have an important role in susceptibility to RVVC. A better understanding of the genetic and immunological mechanisms leading to RVVC is important for both the understanding of the pathophysiology of the disease and the design of novel therapeutic strategies