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© Thierry Blisnick & Philippe Bastin, Institut Pasteur
Bloodstream Trypanosoma brucei cell
Publication : Malaria journal

A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Malaria journal - 09 Nov 2017

Mejia P, Treviño-Villarreal JH, Reynolds JS, De Niz M, Thompson A, Marti M, Mitchell JR,

Link to Pubmed [PMID] – 29121917

Link to DOI – 10.1186/s12936-017-2092-5

Malar J 2017 11; 16(1): 455

Maladaptive immune responses during cerebral malaria (CM) result in high mortality despite opportune anti-malarial chemotherapy. Rapamycin, an FDA-approved immunomodulator, protects against experimental cerebral malaria (ECM) in mice through effects on the host. However, the potential for reduced adaptive immunity with chronic use, combined with an incomplete understanding of mechanisms underlying protection, limit translational potential as an adjunctive therapy in CM.The results presented herein demonstrate that a single dose of rapamycin, provided as late as day 4 or 5 post-infection, protected mice from ECM neuropathology and death through modulation of distinct host responses to infection. Rapamycin prevented parasite cytoadherence in peripheral organs, including white adipose tissue, via reduction of CD36 expression. Rapamycin also altered the splenic immune response by reducing the number of activated T cells with migratory phenotype, while increasing local cytotoxic T cell activation. Finally, rapamycin reduced brain endothelial ICAM-1 expression concomitant with reduced brain pathology. Together, these changes potentially contributed to increased parasite elimination while reducing CD8 T cell migration to the brain.Rapamycin exerts pleotropic effects on host immunity, vascular activation and parasite sequestration that rescue mice from ECM, and thus support the potential clinical use of rapamycin as an adjunctive therapy in CM.

https://pubmed.ncbi.nlm.nih.gov/29121917