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 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<sup>+</sup> 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.
Authors
- Lindsey A. Shallberg (ORCID: https://orcid.org/0000-0001-6573-7327)
- Sambamurthy Chandrasekaran (ORCID: https://orcid.org/0000-0002-2443-2794)
- Christopher A. Hunter (ORCID: https://orcid.org/0000-0003-3092-1428)
- Florence Dzierszinski
- Molly Bunkofske (ORCID: https://orcid.org/0000-0003-1457-5641)
- Emily F. Merritt (ORCID: https://orcid.org/0000-0002-9449-4683)
- Aaron Winn (ORCID: https://orcid.org/0000-0002-0441-9189)
- Maxime Jacquet (ORCID: https://orcid.org/0000-0003-0690-1232)
- Christoph Konradt (ORCID: https://orcid.org/0000-0003-4408-6769)
- David A. Christian (ORCID: https://orcid.org/0000-0002-7160-9900)
- Daniel L. Aldridge (ORCID: https://orcid.org/0000-0003-2224-5159)
- Sebastian Lourido (ORCID: https://orcid.org/0000-0002-5237-1095)
- Eleni Katifori (ORCID: https://orcid.org/0000-0002-7332-4749)
- Christopher J. Giuliano (ORCID: https://orcid.org/0000-0002-0586-6095)
- Julia Eberhard (ORCID: https://orcid.org/0009-0008-5134-9671)
- Anita A. Koshy (ORCID: https://orcid.org/0000-0001-8705-3233)
- Elinor Willis (ORCID: https://orcid.org/0000-0003-0588-9964)
Institutions
- University of Arizona (US)
- Purdue University West Lafayette (US)
- Royal Ottawa Mental Health Centre (CA)
- Flatiron Health (United States) (US)
- Whitehead Institute for Biomedical Research (US)
- Flatiron Institute (US)
- Massachusetts Institute of Technology (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Microbiology
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1038/s41564-025-01967-z
- Citations
- 10
- Primary Topic
- Toxoplasma gondii Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 20.48
Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases