WEHI MINTI Special Seminar hosted by Dr Cyril Seillet
Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 – CNRS UMR5051 – Université Toulouse III
Sex differences in nucleic acid sensing across ages: role of sex hormones and X chromosome
Virtual presentation only
Including Q&A session
Monthly International Immunology Seminar Series (MINTI)
Severe forms of COVID-19 are more common in men than in women in all countries examined so far. It has been proposed that the sex bias in COVID-19 severity might be related to a relative deficiency in innate-immunity to viruses in males compared to females. Toll-like receptor 7 (TLR7), encoded by an X-linked gene, is key to the innate defense against RNA viruses, including SARS-CoV2, and the TLR7-driven innate and adaptive B cell immunity to RNA viruses are stronger and of better quality in females compared to males. TLR7 deficiency due to loss-of-function variants has been identified in patients with severe COVID-19, and are associated with suppressed production of type I interferons (IFN-I) by plasmacytoid dendritic cells (pDCs). Thus, TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Remarkably, the capacity of female pDCs to produce higher levels of IFN-I, compared to those of males, is one immune characteristic that robustly distinguishes the two sexes. I will discuss the findings supporting the notion that both estrogen-signaling and X-linked genetic factors independently contribute to the female predominance in pDC innate functions, and present recent development on the analysis of the sex differences in TLR7-driven interferogenesis across ages.
Jean-Charles Guéry currently holds a position of Research Director at the French Institute of Health and Medical Research (INSERM) at the Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY). He is the Principal Investigator of the Team “Sex differences in immunity: mechanisms and pathophysiology". He received his PhD in Immunology in 1990 at Diderot University in Paris. During his post-doctoral research experience in Sandoz (Basel, Switzerland) and then Hoffman-La Roche (Milan, Italy) he studied several aspects of self and non-self antigen presentation by dendritic cells in vivo and their impact on tolerance induction and adaptive T cell immunity. He established his own group at INSERM, University of Toulouse in 1995. Over the past 20 years, he focused his research interest in the understanding of the mechanisms responsible for sex-related differences in immunity. Recent works in his lab sustain the hypothesis that sex hormones and sex-chromosome loci, may act in a cell-intrinsic manner to regulate the development, maintenance or functional responses of specific cellular subsets of the innate and adaptive immune system, thereby controlling the sex differences in immune related disorders (allergy, autoimmunity, susceptibility to infections).