Deficiency in indoleamine-2, 3-dioxygenase induces upregulation of guanylate binding protein 1 and inducible nitric oxide synthase expression in the brain during cerebral infection with Toxoplasma gondii in genetically resistant BALB/c mice but not in genetically susceptible C57BL/6 mice

We examined the roles of indoleamine-2, 3-dioxygenase 1 (IDOL) in controlling cerebral Toxoplasma gondii infection in both genetically resistant and susceptible strains of mice. In susceptible C57BL/6 mice, IDO expression was immunohistochemically detected only in a minority (22.5%) of tachyzoite-infected cells in their brains during the later stage of infection. When C57BL-6-background IDO1-deficient (IDO1(-/-)) mice were infected, their cerebral tachyzoite burden was equivalent to those of wild-type (WT) animals. In contrast, in resistant BALB/c mice, IDO expression was detected in a majority (84.0%) of tachyzoite-infected cerebral cells. However, tachyzoite burden in BALB/c-background IDO1(-/-) mice remained as low as that of WT mice, which was 78 times less than those of C57BL/6 mice. Of interest, IDO1(-)(/-) mice of only resistant BALB/c-background had markedly greater cerebral expressions of two other IFN-gamma-mediated effector molecules, guanylate binding protein 1 (Gbpl) and nitric oxide synthase 2 (NOS2), than their WT mice. Therefore, it would be possible that IDO1 deficiency was effectively compensated by the upregulated expression of Gbp1 and NOS2 to control cerebral tachyzoite growth in genetically resistant BALB/c mice, whereas IDO1 did not significantly contribute to controlling cerebral tachyzoite growth in genetically susceptible C57BL/6 mice because of its suppressed expression in infected cells. (C) 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Automated summary

The study examined the role of IDOL in controlling cerebral Toxoplasma gondii infection in genetically resistant and susceptible strains of mice. The results showed that IDO1 deficiency in genetically resistant mice was compensated by the upregulated expression of Gbp1 and NOS2 to control the growth of cerebral tachyzoites. In contrast, IDO1 did not significantly contribute to controlling cerebral tachyzoite growth in genetically susceptible mice due to its suppressed expression in infected cells.