Researchers at the Insect Models of Innate Immunity Laboratory (CNRS) have demonstrated an original mechanism for recognizing infections in the Drosophila model organism. It allows detection of the activity of microbial enzymes responsible for virulence, rather than specific molecular patterns found in microorganisms, which constitute “non-self” signals. These results were published on February 15, 2018 in the journal Molecular Cell.
Innate immunity, common to all living organisms, is the first barrier to infection. To defend oneself, the recognition of pathogens is a crucial step. In the results that have just been published, F. Veillard, J.-M. Reichhart and their collaborators identify a molecular mechanism that allows the detection of pathogenic microbes in Drosophila flies. They show for the first time how an innate immunity receptor, Persephone, can be activated by a danger signal, in this case the microbial enzymatic activities responsible for virulence.
The mechanism of activation for the Persephone receptor decrypted
The receptor Persephone is itself a protease; it has a unique region that functions as a bait for all proteases foreign to the body, regardless of their origin, type or specificity. A cut in this region is not enough to activate Persephone, but is the first step of a sequential activation: it allows to recruit another circulating molecule of the family of cathepsins, which will generate the active form of Persephone. Once active, the latter transmits the signal leading to the activation of the Toll receptor and the immune response. This work shows for the first time how an innate immunity receptor, Persephone, can be activated by the enzymatic activity of pathogens.
These results could lead to the identification of related mechanisms in mammals. Such mechanisms, if they exist, could partly explain how the human immune system is able to differentiate between pathogenic bacteria and fungi and harmless microorganisms such as those constituting the microbial flora.
Figure : The circulating protease Persephone is a receptor for proteases secreted by pathogens, leading to activation of the Toll pathway of innate immunity in drosophila. Persephone activates the enzyme SPE, which triggers the maturation of the cytokine Spaëtzle and the activation of the Toll receptor. © Florian Veillard.
The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway. Molecular Cell. Najwa Issa, Nina Guillaumot, Emilie Lauret, Nicolas Matt, Christine Scaeffer-Reiss, Alain Van Dorsselaer, Jean-Marc Reichhart and Florian Veillard.
Molecular Cell, 69 (4), p. 539-550, 2018, ISSN: 1097-2765. doi:10.1016/j.molcel.2018.01.029
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