AUTHOR=Hai Lei , Shi Xiaoyu , Wang Qian 

TITLE=Attenuated T Cell Responses Are Associated With the Blockade of Cerebral Malaria Development by YOP1-Deficient Plasmodium berghei ANKA

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.642585

DOI=10.3389/fimmu.2021.642585

ISSN=1664-3224

ABSTRACT=<p>Reticulon and the REEP family of proteins stabilize the high curvature of endoplasmic reticulum tubules. The REEP5 homolog in <italic>Plasmodium</italic>, <italic>Plasmodium berghei</italic> YOP1 (<italic>Pb</italic>YOP1), plays an important role in the erythrocytic cycle of the <italic>P. berghei</italic> ANKA and the pathogenesis of experimental cerebral malaria (ECM), but the mechanisms are largely unknown. Here, we show that protection from ECM in <italic>Pb</italic>yop1Δ-infected mice is associated with reduced intracerebral Th1 accumulation, decreased expression of pro-inflammatory cytokines and chemokines, and attenuated pathologies in the brainstem, though the total number of CD4<sup>+</sup> and CD8<sup>+</sup> T cells sequestered in the brain are not reduced. Expression of adhesive molecules on brain endothelial cells, including ICAM-1, VCAM-1, and CD36, are decreased, particularly in the brainstem, where fatal pathology is always induced during ECM. Subsequently, CD8<sup>+</sup> T cell-mediated cell apoptosis in the brain is compromised. These findings suggest that <italic>Pb</italic>yop1Δ parasites can be a useful tool for mechanistic investigation of cerebral malaria pathogenesis.</p>