Decoding the role of endogenous retroviruses in controlling type 2 immunity

• Grant number: 23/09270-2
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2025
• End date: January 31, 2030
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Djalma de Souza Lima Júnior
• Grantee: Djalma de Souza Lima Júnior
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Andrea de Cássia Vernier Antunes Cetlin ; Fabrício Marcus Silva Oliveira ; Pedro Henrique Gazzinelli Guimaraes ; Tathiane Maistro Malta Pereira ; Tiago da Silva Medina ; Vânia Luiza Deperon Bonato ; Yasmine Belkaid
• Associated scholarship(s): 25/05025-9 - Investigating the Role of Endogenous Retroviruses in helminth infection under High Fat Diet Conditions., BP.IC; 25/05032-5 - Impact of saturated fatty acid on endogenous retroelements reactivation during atopic dermatitis., BP.IC; 25/04941-1 - Laboratory routine training, BP.TT; 25/03909-7 - Decoding the role of endogenous retroviruses in controlling type 2 immunity., BP.JP

Abstract

All mammals contain and evolved with a multitude of microorganisms. These include the commensal microbiota that colonize barrier surfaces, such as the skin, respiratory, and gastrointestinal tracts, and endogenous retroelements, such as the endogenous retroviruses (ERVs) that comprise a substantial fraction of the mammalian genome. These complex microbial communities profoundly influence host physiology as well as numerous aspects of the immune system. However, environmental perturbations such as antibiotic usage or dietary changes can alter either the composition of the commensal microbes (dysbiosis) or endogenous elements expression and thereby contribute to a variety of human diseases, including inflammatory and infection diseases. Strong Type 2 inflammatory responses are triggered by helminth parasites but also drive allergic disorders. Lung and skin commensals have been reported to protect against allergic and helminth driven Type 2 inflammation by playing an important role in tuning the immune responses to environmental allergens and helminth's antigens. In addition, studies have been shown that changes in the microbiome composition caused by diet changes, in particular high-fat diet feeding, is linked to the increased severity and prevalence of allergic inflammation and Type 2 immune responses. Despite these observations, the processes involved in the initiation and regulation of Type 2 immunity, as well as the mechanisms by which the endogenous virome regulates this response, determining the outcome of type 2-associated inflammatory diseases, remain unknown. Therefore, this proposal aims at understanding of how the endogenous virome and nutritional factors impact Type 2 immune responses during steady-state and inflammation. The long-term goal of this proposed research platform is to identify pathways that trigger the regulation of antigen/allergen-driven Th2 cells responses envisioning to understand the mechanisms underlying the Th2-associated immunity and pathogenesis of both allergic disorders and helminth infections. (AU)