Role of PD-1 pathway in TRM development and function

• Grant number: 15/00680-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: August 08, 2015
• End date: August 07, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: José Maria Álvarez Mosig
• Grantee: Raíssa Fonseca
• Supervisor: David Masopust
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Minnesota (U of M), United States
• Associated to the scholarship: 14/03802-3 - Analysis of the modulatory role of PD-1/PD-L1 interaction in the chronic phase of the murine infection with Trypanosoma cruzi, BP.DD

Abstract

Tissue resident memory (TRM) cells are newly discovered type of T cell memory cell, which is characterized by not recirculating through lymphoid organs and blood, but by being restricted to non lymphoid organs where several infectious agents are concentrated. Considering this, these cells are responsible for beginning the specific response upon reinfection, starting the signals for inflammation and recruitment of other memory cells. In chronic diseases, TRM cells show PD-1 expression, a general marker of exhaustion in CD8+ cells. It is not known, however, how PD-1 influences TRM formation and how it limits TRM and recruited cells response to reinfection. In this project, we will evaluate the importance of PD-1 pathway in the development of TRM cells, through antibody-mediated PD-1 blockage in the beginning of Trypanosoma cruzi (Y Strain) and lymphocytic coriomeningitis virus (LCMV) infection. We will also verify the role of this pathway in inhibiting the immune response of established TRM cells and of recruited cells in the affected tissues, through PD-1 blockage in later points after T. cruzi and LCMV infection. These results will give us the necessary knowledge to improve the study of TRM cells in experimental Chagas disease, which is not described in our model yet, helping to clarify an important part of my PhD project in Brazil. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FONSECA, RAISSA; BEURA, LALIT K.; QUARNSTROM, CLARE F.; GHONEIM, HAZEM E.; FAN, YIPING; ZEBLEY, CAITLIN C.; SCOTT, MILCAH C.; FARES-FREDERICKSON, NANCY J.; WIJEYESINGHE, SATHI; THOMPSON, EMILY A.; et al. Developmental plasticity allows outside-in immune responses by resident memory T cells. NATURE IMMUNOLOGY, v. 21, n. 4, FEB 2020. (15/00680-7)