Chronic infection by atypical Toxoplasma gondii strain induces disturbance in microglia population and altered behaviour in mice

Brito, Ramayana Morais de Medeiros; da Silva, Maria Carolina Machado; Vieira-Santos, Flaviane; de Almeida Lopes, Camila; Souza, Jorge Lucas Nascimento; Bastilho, Alexandre Lazoski; de Barros Fernandes, Heliana; de Miranda, Aline Silva; de Oliveira, Antônio Carlos Pinheiro; de Almeida Vitor, Ricardo Wagner; de Andrade-Neto, Valter Ferreira; Bueno, Lilian Lacerda; Fujiwara, Ricardo Toshio; Magalhães, Luísa Mourão Dias

doi:10.1016/j.bbih.2023.100652

Cited by 4 publications

(3 citation statements)

References 89 publications

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“…A previous study has shown that C1q, IL-1α, and TNF-α, secreted by activated microglia, play a role in astrocyte polarization 18 . Chronic infection with an atypical T. gondii strain can lead to changes in the microglia population and altered behavior in mice 30 . Our study assessed the concentrations of IL-1α and TNF-α in the mouse brain by using ELISA.…”

Section: Resultsmentioning

confidence: 99%

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Yao,

Yuan,

Sheng

et al. 2024

Sci Rep

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Toxoplasma gondii (T. gondii) is a protozoan parasite that infects approximately one-third of the global human population, often leading to chronic infection. While acute T. gondii infection can cause neural damage in the central nervous system and result in toxoplasmic encephalitis, the consequences of T. gondii chronic infection (TCI) are generally asymptomatic. However, emerging evidence suggests that TCI may be linked to behavioral changes or mental disorders in hosts. Astrocyte polarization, particularly the A1 subtype associated with neuronal apoptosis, has been identified in various neurodegenerative diseases. Nevertheless, the role of astrocyte polarization in TCI still needs to be better understood. This study aimed to establish a mouse model of chronic TCI and examine the transcription and expression levels of glial fibrillary acidic protein (GFAP), C3, C1q, IL-1α, and TNF-α in the brain tissues of the mice. Quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay, and Western blotting were employed to assess these levels. Additionally, the expression level of the A1 astrocyte-specific marker C3 was evaluated using indirect fluorescent assay (IFA). In mice with TCI, the transcriptional and expression levels of the inflammatory factors C1q, IL-1α, and TNF-α followed an up-down-up pattern, although they remained elevated compared to the control group. These findings suggest a potential association between astrocyte polarization towards the A1 subtype and synchronized changes in these three inflammatory mediators. Furthermore, immunofluorescence assay (IFA) revealed a significant increase in the A1 astrocytes (GFAP+C3+) proportion in TCI mice. This study provides evidence that TCI can induce astrocyte polarization, a biological process that may be influenced by changes in the levels of three inflammatory factors: C1q, IL-1α, and TNF-α. Additionally, the release of neurotoxic substances by A1 astrocytes may be associated with the development of TCI.

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Section: Resultsmentioning

confidence: 99%

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Yao,

Yuan,

Sheng

et al. 2024

Sci Rep

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“…First, we revisited the question: What will be changed in body when chronic T. gondii infection occurred, and in what aspects do these changes differentiate the host from normal individuals. T. gondii chronic infection impacts the levels of neurotrophic factors and inflammatory mediators in different brain regions, leading to behavioral alterations in mice [ 33 ]. In conjunction with our research, in the common 41 inflammatory factors, T. gondii infection leads to a decrease in the expression levels of IP10, MCP1, and TRAIL.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii infection and brain inflammation: A two-sample mendelian randomization analysis

Yao,

Shi,

Shu

et al. 2024

Heliyon

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“…Thus, the unbalanced immune response triggered by virulent non-archetypal strains may contribute to the development of severe toxoplasmosis. In our recent study [ 90 ] comparing chronic murine infection caused by a type II (ME-49) strain and a non-archetypal (CK-2) strain (ToxoDB #163), the non-archetypal strain induced higher levels of IFN-γ and TNF-α in brain tissue compared to the archetypal strain. Additionally, our study revealed that infection with the non-archetypal strain altered the levels of neuroinflammatory mediators and led to the development of behaviour indicative of depression and anxiety, indicating a potential link between persistent inflammation and behavioural changes.…”

Section: Toxoplasma Gondii Non-archetypal Strains: Virulence...mentioning

confidence: 99%

Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection

Brito,

de Lima Bessa,

Bastilho

et al. 2023

Parasites Vectors

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Toxoplasma gondii is an intracellular parasite with a worldwide distribution. Toxoplasma gondii infections are of great concern for public health, and their impact is usually most severe in pregnant women and their foetuses, and in immunocompromised individuals. Displaying considerable genetic diversity, T. gondii strains differ widely according to geographical location, with archetypal strains predominantly found in the Northern Hemisphere and non-archetypal (atypical) strains, with highly diverse genotypes, found mainly in South America. In this review, we present an overview of the identification and distribution of non-archetypal strains of T. gondii. Special attention is paid to the strains that have been isolated in Brazil, their interaction with the host immunological response, and their impact on disease outcomes. The genetic differences among the strains are pivotal to the distinct immunological responses that they elicit. These differences arise from polymorphisms of key proteins released by the parasite, which represent important virulence factors. Infection with divergent non-archetypal strains can lead to unusual manifestations of the disease, even in immunocompetent individuals. Graphical Abstract

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Chronic infection by atypical Toxoplasma gondii strain induces disturbance in microglia population and altered behaviour in mice

Cited by 4 publications

References 89 publications

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Observing astrocyte polarization in brains from mouse chronically infected with Toxoplasma gondii

Toxoplasma gondii infection and brain inflammation: A two-sample mendelian randomization analysis

Genetic diversity of Toxoplasma gondii in South America: occurrence, immunity, and fate of infection

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