Effect of CD39 ectonucleotidase on the immunopathology of cerebral malaria and its role in CD8 T lymphocyte infiltration in the central nervous system

Cerebral malaria is characterized by the proliferation of CD4+ T cells with a Th1 profile and CD8+ T cells (CTLs) in the spleen, which migrate to the cerebral microvasculature, promoting blood-brain barrier (BBB) dysfunction. In the parenchyma, CTLs and Th1 cells contribute to the reactivity of glial cells, inducing neuroinflammation, promoting cell death and increasing levels of extracellular ATP (eATP). eATP exerts a danger signal and induces inflammation. In this context, the ENTPDases CD39 and CD73 are responsible for the cleavage of eATP into adenosine, a molecule with immunomodulatory and neuroprotective capabilities. The present work postulates that the ectonucleotidase CD39 can reduce the levels of eATP released during cellular damage and neuroinflammation, degrading this molecule and generating adenosine, with neuroprotective and anti-inflammatory capacity. For this, the experimental model of cerebral malaria will be used from the infection of C57BL6 and ENTPD1-/- mice with Plasmodium berghei ANKA. In order to evaluate the role of CD39 on CD8+ T lymphocytes, CD8-/- mice will be adoptively transferred with these cells, whether or not devoid of CD39. Survival and parasitemia parameters will be evaluated, as well as histological analysis of the spleen and brain, analysis of neuroinflammation, based on immunostaining and phenotyping of glial cells, and lymphocytic infiltrates in the brain.

Project details

Basic Science

Nov 2023 — Jun 2025

Brazil