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Indoleamine 2,3-Dioxygenase Activity During Acute Toxoplasmosis and the Suppressed T Cell Proliferation in Mice

2019; Frontiers Media; Volume: 9; Linguagem: Inglês

10.3389/fcimb.2019.00184

2235-2988

Christoph-Martin Ufermann, Andreas Domröse, Timo Babel, Anne Tersteegen, Sevgi Can Cengiz, Silvia Kathrin Eller, Katrin Spekker-Bosker, Ursula R. Sorg, Irmgard Förster, Walter Däubener,

Adenosine and Purinergic Signaling

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite and belongs to the phylum apicomplexa. T. gondii is of medical and veterinary importance, because T. gondii causes the parasitic disease toxoplasmosis. In human cells the interferon-gamma inducible indoleamine 2,3-dioxygenase 1 (IDO1) is an antimicrobial effector mechanism that degrades tryptophan to kynurenine and thus limits pathogen proliferation in vitro. Furthermore, IDO is described to have immunosuppressive properties, e.g. regulatory T cell differentiation and T cell suppression in humans and mice. However, there is only little known about the role of IDO1 in mice during acute toxoplasmosis. To shed further light on the role of mIDO1 in vivo, we infected mIDO1 deficient (IDO-/-) C57BL/6 mice and adequate wild type (WT) control mice with the T. gondii type II strain ME49 and compared the phenotype of IDO-/- and WT mice during acute toxoplasmosis. During murine T. gondii infection we found mIDO1 mRNA and mIDO1 protein, as well as mIDO1 mediated tryptophan degradation in lungs of WT mice. IDO-/- mice show no tryptophan degradation in the lung during infection. Even though T. gondii is tryptophan auxotroph and rapidly replicating during acute infection, the parasite load was unchanged 7 days post infection in IDO-/- mice compared to WT mice. IDO1 is described to have immunosuppressive properties and since T cell suppression is observed during acute toxoplasmosis we analyzed the involvement of mIDO1. Here, we did not find differences in the intensity of ex vivo mitogen stimulated T cell proliferation between WT and IDO-/-. Concomitant nitric oxide synthase inhibition and interleukin-2 supplementation increased the T cell proliferation from both genotypes drastically, but not completely. In sum we analyzed the involvement of mIDO1 during acute murine toxoplasmosis and found a definite mIDO1 induction. Nevertheless, mIDO1 seems to be functional redundant as an antiparasitic defense mechanism during acute toxoplasmosis in mice. Furthermore, we suggest that the systemic T cell suppression observed during acute toxoplasmosis is influenced by macrophage derived nitric oxide activity and regulatory T cells that evolved independently from mIDO1 activity.