RESUMO
Platelets are immune responsive in many diseases as noted by changes in platelet mRNA in conditions such as sepsis1, atherosclerosis2, COVID-193,4, and many other inflammatory and infectious etiologies5. The malaria causing Plasmodium parasite is a persistent public health threat and significant evidence shows that platelets participate in host responses to infection. Using a mouse model of non-lethal/uncomplicated malaria, P. yoelii XNL (PyNL), infected, but not control mouse platelets expressed Ido1, a rate limiting enzyme in tryptophan metabolism that increases kynurenine at the expense of serotonin. Interferon-gamma (IFNï§) is a potent inducer of Ido1 and mice treated with recombinant IFNï§ had increased platelet Ido1 and IDO1 activity. PyNL infected mice treated with anti-IFNï§ antibody had similar platelet Ido1 and metabolic profiles to that of uninfected controls. PyNL infected mice become thrombocytopenic by day 7 post-infection and transfusion of platelets from IFNï§ treated wild type mice, but not Ido1-/- mice, increased the plasma kynurenine to tryptophan ratio, indicating platelets are a source of post-infection IDO1 activity. We generated platelet specific Ido1 knockout mice to assess the contribution of platelet Ido1 during PyNL infection. Platelet specific Ido1-/- mice had increased death and evidence of lung thrombi which were not present in infected WT mice. Platelet Ido1 may be a significant contributor to plasma KYN in IFNï§ driven immune processes and the loss of platelets may limit total Ido1, leading to immune and vascular dysfunction.