Abstract 124: The Immunometabolic Role Of Platelets In Uncomplicated Malaria Infection
Indoleamine 2,3-dioxygenase
Cerebral Malaria
DOI:
10.1161/atvb.41.suppl_1.124
Publication Date:
2022-05-02T13:59:41Z
AUTHORS (7)
ABSTRACT
The malaria causing Plasmodium parasite is a major public health threat. vivax (P vivax) the cause of uncomplicated (UCM). Platelets are cellular mediators thrombosis and also most numerous immune cells in blood, first responder to infections. Thrombocytopenia frequent complication malaria, decrease platelet count negative predictor disease outcome. Malaria infection elicits strong interferon gamma (IFNγ) response. IFNγ potent inducer indoleamine 2,3-dioxygenase (IDO1) rate-limiting enzyme that catalyzes step Tryptophan (Trp) metabolism kynurenine (Kyn) pathway, shunting Trp away from serotonin production. may be altered as means regulate immunometabolic responses, but mechanisms remain unknown. Our RNA-sequencing data P infected humans yoelii mice showed increased expression genes related metabolism, including IDO1 . role for platelets metabolic pathway regulation poorly explored general, particularly infectious diseases. We introduce novel idea participate immunometabolism infection. Using complementary experimental approaches such liquid chromatography-mass spectrometry, ELISA, PCR, western blot, flow cytometry, we test hypothesis source UCM thrombocytopenia results depletion dysregulation. have discovered regulated responses part dependent on pathways. During there Trp, Kyn metabolites, well decreased plasma serotonin. Platelet transfusions can increase Kyn. Understanding interplay between pathways provide better understanding impact diseases beyond improve improved platelet-directed therapeutics many hematological, metabolic,
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