MRC-FAPESP: defining the role of the hematopoietic parasite reservoir in Plasmodium vivax infection and pathology

Abstract

In this collaborative project with the University of Glasgow, we propose, for the first time, an analysis of an overlooked but critical and still neglected aspect of the cycle of the parasite Plasmodium vivax (Pv), referring to the infection of this pathogen in the potential niches hematopoietic. Here, we will systematically investigate Pv infection in one of the main hematopoietic niches, bone marrow (BM) and spleen compared to peripheral blood (PB). Our hypothesis is that differential signatures of the parasite define changes in the BM, spleen and PB, guided by unique interactions that vary the parasite-host relationship, the host's immune response and the pathological processes that can specifically occur in these compartments. We will combine a series of high performance technologies (single cell RNA-seq, LUMINEX and CYTOF) to develop a molecular and cellular atlas of the parasite-host interaction during a hematopoietic infection. In addition, configurations defined ex vivo will be made to reveal mechanisms related to niche-based infection. These analyzes have the potential to inform new antimalarial treatment strategies, offering targets for chemotherapeutic measures in order to reduce the parasitic burden and / or block transmission, in addition to providing valuable information to improve the understanding of complete aspects of Pv biology. We hope that the findings will add to the ongoing global efforts to eliminate and eradicate malaria. (AU)