Exploring Platelet Ido1 Activity in the Pathogenesis of Plasmodium yoelii Uncomplicated Malaria
Location
Gallaudet University - JSAC Multipurpose Room
Start Date
5-3-2024 9:00 AM
End Date
5-3-2024 9:30 AM
Description
The malaria causing Plasmodium parasite is a major public health threat. Platelets, critical in immune response and clotting, decrease during malaria (thrombocytopenia), impacting infection control. Despite evidence of platelets' involvement in infection response and malaria progression, the specific molecular mechanisms remain unclear. Malaria triggers a powerful interferon gamma (IFNγ) response, which activates indoleamine 2,3-dioxygenase (IDO1). IDO1 redirects Tryptophan (TRP) away from serotonin production by initiating TRP metabolism towards the kynurenine (KYN) pathway. Our platelet RNA-seq data from P. vivax infected humans and P. yoelii infected mice revealed increased expression of TRP metabolism-related genes, including IDO1. Using the mouse model of uncomplicated malaria, P. yoelii infection (PyNL), we found a post-infection increase in platelet Ido1 expression and a depletion of plasma serotonin, accompanied by increased KYN. These data are recapitulated in mice treated with recombinant IFNγ indicating it as the major immune driver of Ido1 activity. PyNL Infected mice treated with anti-IFNγ had similar metabolic profiles to that of uninfected controls. Ido1-/- mice exhibited a similar metabolic phenotype to PyNL infected mice that received anti-IFNγ treatment. Platelet specific-Ido1-/- mice were less resilient to PyNL infection, emphasizing its impact during malaria. Loss of platelet Ido1 during thrombocytopenia might affect overall immune response.
Recommended Citation
Blick-Nitko, Sara, "Exploring Platelet Ido1 Activity in the Pathogenesis of Plasmodium yoelii Uncomplicated Malaria" (2024). Global Year of STEM Sign Language Summit. 2.
https://ida.gallaudet.edu/global_STEM_signlanguage/STEM_signlanguagesummit/day_4/2
Exploring Platelet Ido1 Activity in the Pathogenesis of Plasmodium yoelii Uncomplicated Malaria
Gallaudet University - JSAC Multipurpose Room
The malaria causing Plasmodium parasite is a major public health threat. Platelets, critical in immune response and clotting, decrease during malaria (thrombocytopenia), impacting infection control. Despite evidence of platelets' involvement in infection response and malaria progression, the specific molecular mechanisms remain unclear. Malaria triggers a powerful interferon gamma (IFNγ) response, which activates indoleamine 2,3-dioxygenase (IDO1). IDO1 redirects Tryptophan (TRP) away from serotonin production by initiating TRP metabolism towards the kynurenine (KYN) pathway. Our platelet RNA-seq data from P. vivax infected humans and P. yoelii infected mice revealed increased expression of TRP metabolism-related genes, including IDO1. Using the mouse model of uncomplicated malaria, P. yoelii infection (PyNL), we found a post-infection increase in platelet Ido1 expression and a depletion of plasma serotonin, accompanied by increased KYN. These data are recapitulated in mice treated with recombinant IFNγ indicating it as the major immune driver of Ido1 activity. PyNL Infected mice treated with anti-IFNγ had similar metabolic profiles to that of uninfected controls. Ido1-/- mice exhibited a similar metabolic phenotype to PyNL infected mice that received anti-IFNγ treatment. Platelet specific-Ido1-/- mice were less resilient to PyNL infection, emphasizing its impact during malaria. Loss of platelet Ido1 during thrombocytopenia might affect overall immune response.
Comments
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