Role of TIGIT in the immune response during experimental infection by Paracoccidioides brasiliensis

• Grant number: 24/17738-7
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: March 10, 2025
• End date: April 29, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Pedro Victor da Rocha Lima
• Host Institution: Plataforma de Pesquisa e Medicina Translacional. Fundação Oswaldo Cruz (Fiocruz). Ministério da Saúde (Brasil). Ribeirão Preto , SP, Brazil

Abstract

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by a dimorphic fungus, the main species of which is Paracoccidioides brasiliensis. Furthermore, the fungus is endemic to the Americas. The regulatory immune response is important for a balanced physiological homeostasis in the case of a harmful pro-inflammatory response to the host. This regulatory response of the adaptive immune system can be called immunological tolerance. Some co-inhibition molecules are responsible for this tolerogenic mechanism, such as programmed death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), and they play an important role in fungal infections. The role of regulatory T cells in the control of autoimmune diseases is very well addressed. The characterization and understanding of the function of Treg markers show considerable approaches in the development of treatments and in the understanding of the pathogenesis of autoimmune diseases. One of these markers associated with the immune regulatory and inhibiting response is T-cell immunoglobulin and ITIM domain (TIGIT). Considering that the role of TIGIT in viral infections, as well as tumors and autoimmune diseases, is already present in the literature, the role of TIGIT in infectious diseases caused by bacterial, fungal or protozoan pathogens is still unclear. Considering that the role of TIGIT in the regulation of the immune response is not established in P. brasiliensis infection, the justification for this work is based on evaluating the immune response associated with these cytokines in innate and adaptive immunity, in addition to evaluating the tolerogenic role of both mediators during infection in experimental models at 2 different time points post-infection (acute and pseudochronic phases) of the disease. It is expected that in the absence of the TIGIT molecule, a protective response against the fungal pathogen will occur, which characterizes a phenotype of resistance to PCM.