Impact of foetus and mother on IFN-γ-induced indoleamine 2,3-dioxygenase and inducible nitric oxide synthase expression in murine placenta following Toxoplasma gondii infection
Abstract
IFN-gamma production is a hallmark of acute infection with the protozoan parasite Toxoplasma gondii. The tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase (IDO), as well as inducible nitric oxide synthase (NOS2) are induced by IFN-gamma and can play extremely diverse roles in immune regulation, defence against pathogens and physiological homeostasis. We investigated the regulation of these two central enzymes in the placenta during acute infection of pregnant female mice. Using IFN-gamma receptor knockout (IFNgammaR-/-) mice, we showed that IDO is not constitutively expressed in term placentas. In contrast, NOS2 expression was observed, largely dependent on IFN-gamma signalling. Upon infection with the avirulent PRU strain of T. gondii, IDO mRNA expression was induced in an IFNgammaR-dependent manner. Surprisingly, NOS2 mRNA was severely suppressed. Importantly, we showed in crossing experiments of heterozygote (IFNgammaR+/-) mothers with IFNgammaR-/- males and vice versa that IDO expression largely depends on the presence of IFN-gamma receptors on foetal cells, and to a lesser extent on maternal cells. Immunohistochemical analysis localised foetal IDO production to invasive trophoblasts within the maternal part of the placenta. The placental vascular endothelium only stained positive when the mothers possessed functional IFN-gamma receptors. In contrast, placental NOS2 expression, but also its suppression following infection, seems to be largely dependent on IFN-gamma signalling in maternal cells. Neither factor appears to regulate placental T. gondii growth, as we observed no difference in parasite numbers between (+/-) and (-/-) foetuses. Taken together, our results demonstrate the crucial role of the foetus in placental IDO, but not NOS2, production following T. gondii infection.
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Increased kynurenine metabolites have been reported in animal models of maternal inflammation.
“An increase in kynurenine metabolites has been reported in animal models of maternal inflammation (Pfaff et al., 2008; Zavitsanou et al., 2014).”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Pfaff et al., 2008
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Neuroinflammation as a risk factor for attention deficit hyperactivity disorder
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- Authors
- PFAFF, A., MOUSLI, M., SENEGAS, A., MARCELLIN, L., TAKIKAWA, O., KLEIN, J., & CANDOLFI, E.
- Affiliations
- Hôpitaux Universitaires de Strasbourg (FR)
- National Center for Geriatrics and Gerontology (JP)
- Corresponding author
- PFAFF, A
- Venue
- International Journal for Parasitology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 38
- Issue
- 2
- Pages
- 249-258
- ISSN
- 0020-7519 (ISSN-L)
- OpenAlex
- W2040520531
- Cited by
- 23
- References
- 36
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 0.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal for Parasitology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- Toxoplasma gondii, placenta, indoleamine 2,3-dioxygenase, inducible nitric oxide synthase, interferon-gamma signaling, IFN-gamma receptor, pregnancy, tryptophan metabolism, trophoblast
- MeSH terms
- Interferon gamma Receptor, Animals, Female, Fetus, Immunohistochemistry, Interferon-gamma, Mice, Inbred BALB C, Mice, Inbred Strains, Placenta, Pregnancy, RNA, Messenger, Toxoplasma, Toxoplasmosis, Pregnancy Complications, Parasitic, Genes, Protozoan, Receptors, Interferon, Mice, Knockout, Parasitemia, Reverse Transcriptase Polymerase Chain Reaction, Indoleamine-Pyrrole 2,3,-Dioxygenase, Mice, Nitric Oxide Synthase Type II
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