Host Genetic Signatures of Susceptibility to Fungal Disease

Abstract

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.

TSC1 Suppresses Macrophage Necroptosis for the Control of Infection by Fungal Pathogen Candida albicans

“…Being the most common human fungal pathogen, C. albicans has been intensively studied for their pathogenic mechanism and corresponding host countermeasures (50). In this study, we report that TSC1 functions as a critical regulator of macrophage function by controlling their necroptosis upon C. albicans infection.…”

A Case of Invasive Pulmonary Aspergillosis during Treatment for Acute Exacerbation of Interstitial Lung Disease

“…Recently, some genetic defects of the recognition process have been revealed and considered to be a factor of susceptibility to aspergillus infection. 9 As an example, genetic Pentraxin 3 (PTX3) deficiency is known to be a risk factor of invasive aspergillosis. 10 PTX3 is an inflammatory protein activating the toll-like receptor pathway by binding aspergillus conidia.…”

Recent Advances and Novel Approaches in Laboratory-Based Diagnostic Mycology

“…With a significant number of different host mutations associated with increased risk of developing IFD, NGS genetic screening of susceptible patients for mutations predisposing them to a specific fungal disease is possible [ 44 , 45 ]. Given the range of mutations and the fact that most patients will be susceptible to a range of infections, including non-fungal infections, it makes sense to utilize whole genome sequencing to identify a broad range of enhanced genetic risk.…”