Immune targeting and host-protective effects of the latent stage of Toxoplasma gondii

Latency is a microbial strategy for persistence. For Toxoplasma gondii the bradyzoite stage forms long-lived cysts critical for transmission, and its presence in neurons is considered important for immune evasion. However, the extent to which cyst formation escapes immune pressure and mediates persi...

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Published in:Nature microbiology Vol. 10; no. 4; p. 992
Main Authors: Eberhard, Julia N, Shallberg, Lindsey A, Winn, Aaron, Chandrasekaran, Sambamurthy, Giuliano, Christopher J, Merritt, Emily F, Willis, Elinor, Konradt, Christoph, Christian, David A, Aldridge, Daniel L, Bunkofske, Molly E, Jacquet, Maxime, Dzierszinski, Florence, Katifori, Eleni, Lourido, Sebastian, Koshy, Anita A, Hunter, Christopher A
Format: Journal Article
Language:English
Published: England 01.04.2025
Subjects:
Animals
CD8-Positive T-Lymphocytes - immunology
Disease Models, Animal
Host-Parasite Interactions - immunology
Mice
Mice, Inbred C57BL
Models, Theoretical
STAT1 Transcription Factor - immunology
STAT1 Transcription Factor - metabolism
Toxoplasma - growth & development
Toxoplasma - immunology
Toxoplasma - pathogenicity
Toxoplasmosis - immunology
Toxoplasmosis - parasitology
Toxoplasmosis, Animal - immunology
Toxoplasmosis, Animal - parasitology
ISSN:2058-5276, 2058-5276
Online Access:Get more information
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Summary:Latency is a microbial strategy for persistence. For Toxoplasma gondii the bradyzoite stage forms long-lived cysts critical for transmission, and its presence in neurons is considered important for immune evasion. However, the extent to which cyst formation escapes immune pressure and mediates persistence remained unclear. Here we developed a mathematical model highlighting that bradyzoite-directed immunity contributes to control of cyst numbers. In vivo studies demonstrated that transgenic CD8 T cells recognized a cyst-derived antigen, and neuronal STAT1 signalling promoted cyst control in mice. Modelling and experiments with parasites unable to form bradyzoites (Δbfd1) revealed that the absence of cyst formation in the central nervous system did not prevent long-term persistence but resulted in increased tachyzoite replication with associated tissue damage and mortality. These findings suggest the latent form of T. gondii is under immune pressure, mitigates infection-induced damage and promotes survival of host and parasite.
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ISSN:2058-5276
2058-5276
DOI:10.1038/s41564-025-01967-z