Presentation

I am a pediatrician and immunologist by training and have made substantial contributions to the field of genetic predisposition to infectious diseases, including bacterial and mycobacterial infectious diseases, in humans. In my clinical role, I am responsible for the diagnosis of chronic granulomatous disease (CGD) and inborn errors of innate immunity in patients admitted to the Center for the Study of Primary Immunodeficiencies (CEDI) at the Necker Hospital for Sick Children, Paris. My complementary expertise in molecular immunology and human genetics of infectious diseases has enabled me make significant contributions to the field of mycobacterial diseases and inborn errors of immunity affecting the NADPH oxidase complex. Additionally, my work has advanced knowledge of the molecular, cellular, and immunological basis of various infectious diseases and related conditions, encompassing mycobacterial diseases including tuberculosis (mutations in IFNGR1, IFNGR2, IFNG, STAT1, IL12B, IL12RB1, NEMO, IRF8, CYBB, ISG15, TYK2, SPPL2A, IL12RB2, IL23R, RORC, TBX21, ZNFX1, JAK1, USP18, IRF1, MCTS1, CCR2) and Whipple’s disease (IRF4, CD4), invasive pneumococcal disease (NEMO, IRAK4), chronic mucocutaneous candidiasis (IL17F, IL17RC, STAT1), and severe cytomegalovirus disease (NOS2). In collaboration with other groups, I also discovered mutations in NCF4, PRKCD and ARPCB1 underlying noninvasive bacterial infections and inflammatory disease, and in USP18 and STAT2 underlying bacterial diseases and interferonopathies. These studies have important clinical implications, as they provide a basis for genetic counseling and a rationale for developing new therapeutic approaches based on an understanding of the host component of infectious diseases. These studies also have major biological implications, as they reveal the largely redundant function of host defense genes in natura, in the setting of a natural ecosystem governed by natural selection.

Scientific project

The aims of the team is to identify novel Mendelian susceptibility to mycobacterial disease (MSMD) and tuberculosis (TB)-causing genes, and the corresponding immunological mechanisms, in patients lacking a genetic etiology. We dissect the molecular and cellular diversity of defects of IFN- immunity, while considering the possibility to discover novel pathways involved in anti-mycobacterial immunity. We search for and characterize the underlying genetic defects using i) cutting-edge genome-wide strategies, including NGS technologies, and ii) in depth-functional studies to validate the genetic variants identified. The hypothesis tested is that TB develops via a mechanism involving the production of auto-antibodies against IFN-γ.