Prof. Thierry ROGER

Combining basic and translational research, the aim of our team is to decipher the pathophysiological mechanisms of infectious diseases with as ultimate goal the development of new diagnostic and therapeutic weapons for critically ill infected patients. In its endeavor, our team brings together researchers at the crossroads of cellular and molecular biology as well as bioinformatics, the expertise of animal experiments and clinical studies, and the latest technologies in omics. We pay particular attention to mentoring students and passing on knowledge in the fields of innate immunity and host defenses against infections.

MIF, a central regulator of innate immune responses

Macrophage migration inhibitory factor (MIF) was the first cytokine bioactivity reported in 1966. The impact of MIF on innate immune responses have long remained enigmatic. Over the years, we characterized the expression and modes of action of MIF. Among others, we have shown that MIF modulates innate immune responses by acting on the expression of Toll-like receptor 4 (TLR4) and MAPK phosphatase-1, and that elevated MIF blood levels in newborns sustain their innate immune capacities challenging the concept that newborns are purely immunosuppressed. Our translational approach also enabled us to develop tools for immunotherapy targeting MIF in infectious or oncologic diseases.

Host defenses, epigenetic and trained immunity

In the early 2010s, we started to explore the interplay between epigenetic and host defenses. Histone deacetylases (HDACs) are among key enzymes controlling epigenetic modifications, and a subclass of HDACs, the sirtuins, have attracted considerable interest as regulators of lifespan. We performed the first comprehensive study of the impact of HDAC inhibitors (HDACi) on innate immune responses, which is all the more relevant now that drugs of this class are used in oncology patients. We have shown that HDACi impede antimicrobial host defenses, leading us to propose a close immuno-monitoring of treated patients. Next, we were the first to decipher the impact of sirtuins on anti-infectious responses in vivo.

We have recently begun to study the phenomenon of trained immunity which has challenged the dogma that immunological memory is an exclusive property of the adaptive immune system. Indeed, trained immunity reflects the capacity of the innate immune system to adapt to an initial challenge and mount an improved response to a secondary challenge. Manipulating trained immunity offers tremendous translational possibilities in the field of infectious diseases, among others.

Enhancing sepsis management

Sepsis is a life-threatening medical emergency. Sepsis affects 49 million people and is accountable for one in five deaths per year worldwide. On the long-term around one third of survivors develop functional and cognitive impairments. In 2017, the World Health Organization declared sepsis as a global health priority, and provided recommendations for improving prevention, diagnosis and management of sepsis. Participating to that effort, our laboratory has a long-standing expertise in studying host-pathogen interactions, discovery of biomarkers, and testing innovative therapies for infected patients.