Role of TAM Receptors Axl and MerTK in Modulating the Cellular Memory Immune Response to BCG Vaccination

• Grant number: 25/12229-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Diego Luís Costa
• Grantee: Luis Henrique Maia Loiola
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The BCG (Bacillus Calmette-Guérin) vaccine is currently the only licensed vaccine for administration in humans to prevent tuberculosis (TB), caused by the Mycobacterium tuberculosis (Mtb) bacillus. However, the vaccine fails to protect adults against the pulmonary form of TB. Therefore, there is a need to develop strategies to enhance BCG. This undergraduate research project aims to characterize the involvement of tyrosine kinase-coupled receptors Axl and MerTK in modulating the response of dendritic cells (DCs) and how this may interfere with the generation of memory CD4+ T lymphocytes, which are crucial for long-term protection following BCG vaccination. These receptors, once activated in DCs, induce the expression of SOCS 1 and 3, which promote ubiquitination and subsequent degradation of proteins involved in signaling pathways of TLRs (Toll-like receptors) and pro-inflammatory cytokine receptors, such as IL-6, IL-12, TNF alpha, and interferon gamma, thereby negatively modulating the inflammatory and immune response. Additionally, they interfere with the expression of molecules critical for T lymphocyte activation, such as MHC class II and co-stimulatory molecules like CD40 and CD86. Therefore, our hypothesis is that blocking Axl and MerTK receptors in DCs makes BCG immunization more effective in generating a more robust adaptive immune response and capable of developing long-term immunological memory that provides better protection against Mtb infection in adults. (AU)