The interplay between STING and NLRP3 in regulating autophagy.

• Grant number: 24/14194-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2024
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Nicolas Riteau
• Grantee: Viviani Mendes de Almeida
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The STimulator of INterferon Genes (STING) pathway represents a fundamental component of the innate immune system (Hopfner and Hornung 2020), orchestrating the detection of cytosolic DNA and the initiation of immune responses. Typical STING activation initiates a signaling cascade triggering tank-binding kinase 1 (TBK1)/interferonregulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB), leading to the transcription of genes encoding type I interferons (IFNs), cytokines, and mediators pivotal for orchestrating a robust immune response. Originally identified as a defense mechanism against viral and bacterial invasions through its interaction with foreignDNA, recent evidence highlights the involvement of STING in maintaining tissue homeostasis and negatively regulating inflammation under certain conditions (Sharma, Campbellet al. 2015, Ahn, Son et al. 2017, Canesso, Lemos et al. 2018, Lemos, Mohamed et al. 2019, Johnson, Uchimura et al. 2021) . Interestingly, STING displays anti- inflammatory properties through its phylogenetically conserved autophagy-inducing pathway, however the molecular details of this immunoregulatory function are poorly understood. We have generated preliminary data indicating thatNLRP3 is important for STING-mediated autophagy. The objective of this postdoc is to delineate the molecular pathways involved as well as the immune consequences.