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Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route

Toxoplasma gondii is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection (p.o.) of mice with T. gondii is applied to...

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Autores principales: French, Timothy, Steffen, Johannes, Glas, Albert, Osbelt, Lisa, Strowig, Till, Schott, Björn H., Schüler, Thomas, Dunay, Ildiko Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311312/
https://www.ncbi.nlm.nih.gov/pubmed/35898505
http://dx.doi.org/10.3389/fimmu.2022.920658
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author French, Timothy
Steffen, Johannes
Glas, Albert
Osbelt, Lisa
Strowig, Till
Schott, Björn H.
Schüler, Thomas
Dunay, Ildiko Rita
author_facet French, Timothy
Steffen, Johannes
Glas, Albert
Osbelt, Lisa
Strowig, Till
Schott, Björn H.
Schüler, Thomas
Dunay, Ildiko Rita
author_sort French, Timothy
collection PubMed
description Toxoplasma gondii is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection (p.o.) of mice with T. gondii is applied to investigate mucosal and peripheral immune cell dynamics, whereas intraperitoneal infection (i.p.) is frequently used to study peripheral inflammation as well as immune cell – neuronal interaction in the central nervous system (CNS). However, the two infection routes have not yet been systematically compared along the course of infection. Here, C57BL/6 mice were infected p.o. or i.p. with a low dose of T. gondii cysts, and the acute and chronic stages of infection were compared. A more severe course of infection was detected following i.p. challenge, characterized by an increased weight loss and marked expression of proinflammatory cytokines particularly in the CNS during the chronic stage. The elevated proinflammatory cytokine expression in the ileum was more prominent after p.o. challenge that continued following the acute phase in both i.p. or p.o. infected mice. This resulted in sustained microbial dysbiosis, especially after p.o. challenge, highlighted by increased abundance of pathobionts from the phyla proteobacteria and a reduction of beneficial commensal species. Further, we revealed that in the CNS of i.p. infected mice CD4 and CD8 T cells displayed higher IFNγ production in the chronic stage. This corresponded with an increased expression of C1q and CD68 in the CNS and reduced expression of genes involved in neuronal signal transmission. Neuroinflammation-associated synaptic alterations, especially PSD-95, VGLUT, and EAAT2 expression, were more pronounced in the cortex upon i.p. infection highlighting the profound interplay between peripheral inflammation and CNS homeostasis.
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spelling pubmed-93113122022-07-26 Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route French, Timothy Steffen, Johannes Glas, Albert Osbelt, Lisa Strowig, Till Schott, Björn H. Schüler, Thomas Dunay, Ildiko Rita Front Immunol Immunology Toxoplasma gondii is a highly successful parasite capable of infecting all warm-blooded animals. The natural way of infection in intermediate hosts is the oral ingestion of parasite-contaminated water or food. In murine experimental models, oral infection (p.o.) of mice with T. gondii is applied to investigate mucosal and peripheral immune cell dynamics, whereas intraperitoneal infection (i.p.) is frequently used to study peripheral inflammation as well as immune cell – neuronal interaction in the central nervous system (CNS). However, the two infection routes have not yet been systematically compared along the course of infection. Here, C57BL/6 mice were infected p.o. or i.p. with a low dose of T. gondii cysts, and the acute and chronic stages of infection were compared. A more severe course of infection was detected following i.p. challenge, characterized by an increased weight loss and marked expression of proinflammatory cytokines particularly in the CNS during the chronic stage. The elevated proinflammatory cytokine expression in the ileum was more prominent after p.o. challenge that continued following the acute phase in both i.p. or p.o. infected mice. This resulted in sustained microbial dysbiosis, especially after p.o. challenge, highlighted by increased abundance of pathobionts from the phyla proteobacteria and a reduction of beneficial commensal species. Further, we revealed that in the CNS of i.p. infected mice CD4 and CD8 T cells displayed higher IFNγ production in the chronic stage. This corresponded with an increased expression of C1q and CD68 in the CNS and reduced expression of genes involved in neuronal signal transmission. Neuroinflammation-associated synaptic alterations, especially PSD-95, VGLUT, and EAAT2 expression, were more pronounced in the cortex upon i.p. infection highlighting the profound interplay between peripheral inflammation and CNS homeostasis. Frontiers Media S.A. 2022-07-11 /pmc/articles/PMC9311312/ /pubmed/35898505 http://dx.doi.org/10.3389/fimmu.2022.920658 Text en Copyright © 2022 French, Steffen, Glas, Osbelt, Strowig, Schott, Schüler and Dunay https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
French, Timothy
Steffen, Johannes
Glas, Albert
Osbelt, Lisa
Strowig, Till
Schott, Björn H.
Schüler, Thomas
Dunay, Ildiko Rita
Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
title Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
title_full Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
title_fullStr Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
title_full_unstemmed Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
title_short Persisting Microbiota and Neuronal Imbalance Following T. gondii Infection Reliant on the Infection Route
title_sort persisting microbiota and neuronal imbalance following t. gondii infection reliant on the infection route
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311312/
https://www.ncbi.nlm.nih.gov/pubmed/35898505
http://dx.doi.org/10.3389/fimmu.2022.920658
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