Born in Luxembourg in 1941, Hoffmann studied at the Université de Strasbourg where he obtained his Ph.D. in Experimental Biology in 1969. He joined CNRS in 1964 and set up the CNRS laboratory "Réponse Immunitaire et Développement Chez les Insectes" which he headed until 2006. This laboratory is part of the CNRS Institut de Biologie Moléculaire et Cellulaire, which he also directed from 1994 to 2006.
At the start of his career, Hoffmann took an interest, with his collaborators, in the role of steroid hormones on the development and reproduction of insects. His research, conducted at the interface between chemistry and biology, focused on the biosynthesis process, the metabolism and the roles of ecdysone, the hormone that controls insect molting. This work led to the discovery of maternal-fetal transmission of ecdysone.
From the late 1980s, Hoffmann initiated several series of crucial studies making Drosophila (or vinegar fly) a model for innate immunity1
research. With his colleagues, he took a particular interest in antibacterial and antifungal responses. The laboratory researchers discovered and characterized around twenty antimicrobial peptides in Drosophila. They analyzed the gene expression of these peptides during immune response. Among these antimicrobial peptides, some are found in mammals and it is now known that humans also produce them in considerable quantities, particularly in the skin, the digestive tract and the kidneys.
Hoffmann's team made a remarkable discovery in 1996 by demonstrating, using molecular genetics tools, the first transmembrane receptor of innate immunity capable of activating gene expression in the immune system. This receptor, known as Toll, had been initially identified in Germany for its role in the embryonic development of Drosophila.
The work of Hoffmann's laboratory has shown that the Toll receptor is activated in response to a fungal infection (caused by a fungus) or a bacterial infection (by Gram-positive bacteria). Such infection triggers the activation of an intracellular signaling cascade that results in the expression of genes coding in particular for powerful antimicrobial peptides that destroy the fungal or bacterial invaders. American researchers (Charles Janeway at Yale), with whom the Hoffmann group collaborated in the “Human Frontiers in Science” program, searched for homologous receptors in humans. One year later, the existence of a family of human receptors similar to those initially discovered in the antifungal response of Drosophila was established. Named “Toll-Like Receptors” (TLR), these human receptors participate in the activation and amplification of the specific, adaptive immune response, which characterizes vertebrates.
Researchers from Hoffmann's laboratory have also discovered the existence of a second immune response process in Drosophila that essentially responds to infections by Gram-negative bacteria. This process (known as IMD for Immune Deficiency) is distinct from that of Toll/TLR receptors and is similar to the tumor necrosis factor (TNF)2
process in humans.
By demonstrating the marked conservation of innate defense mechanisms between insects and humans, the work initiated by Hoffmann and his collaborators has led to a re-evaluation of the role of innate immunity in mammals, which has widely contributed to the resurgence in interest in this somewhat neglected field of immunology. Immunity studies on insects have had considerable repercussions and the research conducted at the CNRS laboratory “Réponse Immunitaire et Développement Chez les Insectes" now extends to antiviral reactions in Drosophila and the antiparasitic defenses of the Anopheles mosquito, the vector of malaria. More generally, the Drosophila model has enabled biologists throughout the world to make considerable progress, not only in development genetics and innate immunity but also in the study of certain human pathologies and in the understanding of memory, behavior, sleep and nutrition phenomena.
President of the Académie des Sciences Française in 2007 and 2008, Hoffmann is also a member of the Academy of Sciences of the United States of America, Germany and Russia. He has been awarded numerous prestigious prizes, such as, in recent years, the Rosenstiel Award for his work on immunity (2010), the Keio Medical Science Prize (2011), the 2011 Gairdner Award for medical research and the 2011 Shaw Prize in Life Science and Medicine. Hoffmann has also been made "Chevalier de la Légion d'Honneur" in France.
© Pascal Disdier/CNRS Photothèque
(1) Innate immunity is a front-line antimicrobial defense mechanism that immediately comes into action against microbial agents that have come into contact with an organism. Devoid of the particular specificity of adaptive immunity and the phenomenon of memory, which forms the basis of vaccination, innate immunity exists in all living organisms and plays a vital role in the activation of the adaptive response in vertebrates.
(2) TNF (tumor necrosis factor) is an inflammatory cytokine indispensable for immune defense against pathogens. Cytokines are molecules that play the role of cell mediator.