My research seeks to understand why exposure to the same microorganism can remain asymptomatic in most individuals yet cause severe or life-threatening disease in others. By investigating patients with unexplained, rare, severe, and/or recurrent infections, we aim to uncover the genetic and immunological mechanisms that account for this striking interindividual variability and to define the non-redundant components of human host defense under natural conditions of infection.
A major focus of my work is human antifungal immunity. We study patients with chronic mucocutaneous candidiasis, invasive candidiasis, deep dermatophytosis, cryptococcosis, and other severe fungal diseases to identify novel inborn errors of immunity and determine how the affected genes and pathways protect humans against fungal infection. This work has revealed the essential role of IL-17 immunity in mucocutaneous defense against Candida albicans and established CARD9-dependent immunity as a central mechanism of protection against invasive fungal diseases. We continue to investigate how defects affecting immune and non-immune cells shape susceptibility to specific fungal pathogens and clinical manifestations.
A second major research axis concerns autoantibodies that neutralize cytokines and are acquired phenocopies of inborn errors of immunity. We investigate how these autoantibodies arise, why they develop in some individuals, and how they impair protection against viral, bacterial, or fungal infections. Particular attention is given to autoantibodies against type I interferons and other cytokines with essential roles in host defense. Our objective is to identify the genetic, immunological, and clinical factors associated with their development and to determine their value as biomarkers of infectious risk.
By moving from the investigation of individual patients to the discovery of general mechanisms of human immunity, our research aims to improve the recognition of previously unexplained infectious diseases and support more accurate diagnosis, risk stratification, prevention, and personalized therapeutic management.