À propos
I am an INSERM Research Director (DR1) at the Imagine Institute and Université Paris Cité, where I lead the “Human Genetic and Immunological Determinants of Fungal Diseases” group and co-lead the “Anti-Cytokine Autoantibodies” group within the Laboratory of Human Genetics of Infectious Diseases.
Trained in immunology, genetics, and infectious diseases, I investigate the genetic and immunological mechanisms underlying otherwise unexplained susceptibility to infection in humans. My research is based on the study of patients with rare, severe, and/or recurrent infectious diseases, whose clinical phenotypes can reveal essential and non-redundant mechanisms of host defense under natural conditions of infection.
My work has made major contributions to our understanding of human immunity to bacterial, fungal, and viral infections. In particular, it has helped establish the essential role of IL-17-mediated immunity in protection against chronic mucocutaneous candidiasis and identify CARD9 deficiency as a major genetic cause of invasive fungal diseases.
I also study autoantibodies that neutralize cytokines and thereby create acquired phenocopies of inborn errors of immunity. These autoantibodies can disrupt otherwise intact immune pathways and predispose previously healthy individuals to severe or life-threatening bacterial, fungal, or viral infections. By investigating their origins, underlying mechanisms, and clinical consequences, my research aims to improve the diagnosis, risk assessment, and personalized management of patients with severe infectious diseases.
ORCID 0000-0003-2603-0323
https://pubmed.ncbi.nlm.nih.gov/?term=puel+a&sort=date
Projet scientifique
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.
2024Journal (source)J Exp Med