Immune mechanisms determinant of anemia in Plasmodium vivax infections: Understanding the role of the destruction of uninfected erythrocytes

Anemia associated with malaria has been the subject of few studies and, therefore, its etiology is not yet fully understood. Among the factors that contribute to anemia are the hemoglobin digestion and the destruction of the red blood cells, immediate developmental results and multiplication of the parasite during its life cycle. However, these factors alone do not explain this clinical manifestation, since, in endemic areas, the degree of anemia does not always correlate with the detected parasitemias. In P. vivax infections, a species that has the biological preference of infecting reticulocytes, which constitute only 1-2% of circulating cells, this lack of correlation is even more evident. Mathematical models have estimated that, during vivax malaria, about 32 normal red blood cells are destroyed for each parasitic hemocyte, suggesting that this destruction of normal red blood cells may be the main cause of anemia. However, the immune mechanisms involved in this process are not well understood. The effects of antibodies from patients with severe and non-severe vivax malaria, with or without anemia, will be analyzed. The role of cytokines (IL-4, IL-10 and TNF-α) in modulating the effects caused by antibody binding on the surface of uninfected erythrocytes will also be evaluated. These effects will be analyzed from different approaches, for example, defocus microscopy, a powerful and promising technique that allows to obtain total three-dimensional images, besides the precise characterization of the morphological and biomechanical properties of the cell. In addition, it is intended to evaluate the effects of the binding of antibodies to the surface of healthy erythrocytes on the band 3 protein-dependent transport of ions, using a fluorescent probe for halides to measure the exchange of ions Chloride by bicarbonate ions in membrane ghosts. It will also use in vitro erythrophagocytosis assays to measure the effect of opsonization and the addition of cytokines on the rate of phagocytosis of normal erythrocytes. Finally, this project will investigate the possible association between the ABO phenotype and anemia in P. vivax infections, a subject that is still little explored and understood. All of this information will broaden the understanding of the mechanisms involved in determining anemia in P. vivax infections and may direct scientific research to the development of new malaria treatments and vaccines.

Immunology
P. vivax

Jun 2017 — May 2020

Brazil