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Contact

Claudine Boiziau

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Contact

Linkedin biotis-bordeaux

Secretary Email

33 (0)5 57 57 14 88

Bioingénierie Tissulaire (BioTis)       

Physical Address:

Batiment BBS (Bordeaux Biologie Santé), 5e étage

2, rue du Dr Hoffmann Martinot,

33000, Bordeaux, France

Mailing Address:

Université de Bordeaux, Campus Carreire

146, rue Léo Saignat, Case 84,

33076, Bordeaux Cedex, France

Foreign Body Reaction and regulation of macrophage activation by autophagy

Abstract

Reference

Project Leader

Macrophages have acquired the status of cells playing a key role in the foreign body reaction (FBR) and in tissue regeneration following the implantation of a medical device (Brown et al., 2012) (Oliveira et al., 2016). In 2002, the concept of inflammasomes was proposed (Martinon et al., 2002): these are a family of complexes formed by cytosolic proteins (of which NLRP3 is the most studied) that assemble in the cytoplasm in response to bacterial infection, cell damage, and other danger signals (He et al., 2016); Inflammasomes are involved in innate immunity and enable the maturation and secretion of IL1β and IL18 associated with the pro-inflammatory phenotype of macrophages.




Dysregulations of inflammasomes are associated with inflammatory diseases such as Crohn's disease and multiple sclerosis, as well as Alzheimer's disease, diabetes, and atherosclerosis (Kelley et al., 2019). FBR induced by the implantation of a biomaterial has also been shown to be linked to inflammasome activation (Christo et al., 2016). Autophagy has been shown to be a regulatory system for the inflammasome, either by eliminating the factors that activate it (damaged mitochondria or phagosomes) or by degradation of the inflammasome proteins (Saitoh and Akira, 2016; Biasizzo and Kopitar-Jerala, 2020).

This project aims at studying inflammasome regulation by autophagic processes after a device sub-cutaneous implantation.

▷Biasizzo, M., Kopitar-Jerala, N., 2020. Interplay Between NLRP3 Inflammasome and Autophagy. Front. Immunol. 11, 591803. https://doi.org/10.3389/fimmu.2020.591803

▷Brown, B.N., Ratner, B.D., Goodman, S.B., Amar, S., Badylak, S.F., 2012. Macrophage polarization: An opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 33, 3792–3802. https://doi.org/10.1016/j.biomaterials.2012.02.034

▷Christo, S.N., Diener, K.R., Manavis, J., Grimbaldeston, M.A., Bachhuka, A., Vasilev, K., Hayball, J.D., 2016. Inflammasome components ASC and AIM2 modulate the acute phase of biomaterial implant-induced foreign body responses. Sci Rep 6, 20635. https://doi.org/10.1038/srep20635

▷He, Y., Hara, H., Núñez, G., 2016. Mechanism and Regulation of NLRP3 Inflammasome Activation. Trends Biochem. Sci. 41, 1012–1021. https://doi.org/10.1016/j.tibs.2016.09.002

▷Kelley, N., Jeltema, D., Duan, Y., He, Y., 2019. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. IJMS 20, 3328. https://doi.org/10.3390/ijms20133328

▷Martinon, F., Burns, K., Tschopp, J., 2002. The Inflammasome. Mol. Cell 10, 417–426. https://doi.org/10.1016/S1097-2765(02)00599-3

▷Saitoh, T., Akira, S., 2016. Regulation of inflammasomes by autophagy. J. Allergy Clin. Immunol. 138, 28–36. https://doi.org/10.1016/j.jaci.2016.05.009