Evaluation of the role of CD8+ T lymphocytes in recognition of proteins expressed in reticulocytes infected with Plasmodium vivax

• Grant number: 21/12851-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): December 01, 2021
• Effective date (End): May 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: Osvaldo Campos dos Santos Nonato
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/23618-8 - Immunological mechanisms of resistance and disease in malaria, AP.TEM

Abstract

In the last 15 years, my lab has dedicated to understand the mechanisms by which Plasmodium infection stimulate the innate immune responses and what is the outcome of these responses in host resistance to infection and pathogenesis of . The current research program includes three projects around a maintheme, which is "Immunological mechanisms of host resistance and disease in Malaria". In the first project titled "Monocyte Dendritic Cells (MO-DCs) in Malaria", we plan to evaluate the emergence of MO-DCs and the their pathogenic role in rodent Malaria. In the second project titled "Killing of P. Vivax infected reticulocytes by cytotoxic T cells" we provide evidences that P. vivax infected reticulocytes express HLA-I (MHC class I) and are killed by CD8+ T cells from Malaria patients. We intent to evaluate the competence of reticulocytes to present endogenous antigens via HLA-I and the mechanism of intracelular parasite killing by CD8+ cytotoxic T cells. Finally, third project is titled "Immunology of asymptomatic Malaria and the effects of immunity on Plasmodium transmission". In this project, we propose to identify innate immune biomarkers as well as B and T cell responses that are predictive of disease outcome and mosquito transmission. If successful, our studies will provide important information for monitoring silent infection in infective asymptomatic individuals and potentially new insights to further control Malaria transmission in hypo-endemic areas. In summary, by using ex vivo, in vitro and in vivo experimental models, we intent to elaborate cell biology and immunological questions that will allow us to address the mechanisms of host resistance and pathogenesis of Malaria. In the third project we intent to apply some of the hypothesis raised in the lab to define mechanisms that are potentially involved in modulating the systemic inflammation and preventing parasite elimination in asymptomatic Malaria patients, and therefore, main impediment for eliminating parasite transmission in hypo-endemic areas of Malaria. (AU)