Host-parasite interactions during infection in the hematopoietic niche in malaria: in vitro assays for the evaluation of Plasmodium reticulocyte

• Grant number: 22/02080-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2022
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: João Pedro da Cunha Tavares
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax, AP.TEM

Abstract

Malaria remains a global health problem. According to estimates by the World Health Organization in 2020, approximately 241 million cases and 627 thousand deaths were recorded. Among the species that cause human malaria, Plasmodium vivax is the species that has the highest geographic distribution in addition to being the most prevalent species outside the African continent. Brazil is the 2nd country with the highest number of cases in the Americas, with 99.5% of them reported in the Amazonas region, with P. vivax being responsible for 80% of the cases. Unique biological features of P. vivax complicate its treatment and elimination, including the rapid appearance of transmissible forms (gametocytes) in the bloodstream and the presence of dormant liver stages (hypnozoites), which recur weeks or months after the blood infection is cleared. In addition, there is the low peripheral parasitemia of P. vivax (generally less than 2%) is the result of a strict tropism by immature reticulocytes like cell hosts, most of them present in the hematopoietic system. The enrichment of asexual stages and gametocytes in the hematopoietic niche of the bone marrow has already been identified in human autopsies of patients infected with P. falciparum and in infected mice with P. berghei. Several pieces of evidence also suggest that, in P. vivax infections, parasitemia peripheral represents only a fraction of the total parasite biomass, while the majority accumulates in the hematopoietic system. Furthermore, a recent and comprehensive analysis of P. berghei infection was performed using flow cytometry assays and single-cell RNA sequencing. CD71 has been identified as a host receptor for reticulocyte invasion and the parasites metabolically adapt to the cell environment host. Transcriptional analysis and functional assays also revealed a dependent tropism of nutrients for the formation of gametocytes in reticulocytes. One of the objectives of the thematic project to which this project is linked is to understand a host-parasite in a hematopoietic niche. Thus, in the current proposal, we will seek to establish crucial assays for the characterization of reticulocytes and their precursors present in the bone marrow, as well as for the evaluation of the interaction of Plasmodium in this environment.(AU)