T cell responses in repeated controlled human schistosome infection compared to natural exposure
In Schistosoma-endemic regions a lack of natural sterilizing immunity means individuals are repeatedly infected, treated and reinfected. Due to difficulties in tracking natural infection, kinetics of host immune response during these reinfections have not been elucidated. Here, we use repeated (3x) controlled-human-Schistosoma mansoni infection (CHI) to study how antigen-specific T cells develop during reinfection (NCT05085470 study). We compared these responses to naturally infected endemic Ugandan individuals (HALLMARK study). A mixed Th1/Th2/regulatory CD4<sup>+</sup> T cell response develops in repeated CHI. Adult-worm-specific responses after repeated CHI were similar to endemic-natural infection. However, endemic participants showed differential responses to egg- and cercariae-antigens. Repeated CHI with sequential exposure to cercariae of different sexes (male-female-male) revealed an elevated CD4<sup>+</sup> T cell cytokine response to adult-worm and egg-antigens. Our findings demonstrate that single-sex schistosome infection elicits adult-worm-specific T cell cytokine responses that reflect endemic-natural infection. This study advances our understanding of the immunology of schistosome (re)infection in the human host.
Authors
- Irene Nambuya
- Jacqueline J. Janse (ORCID: https://orcid.org/0000-0003-4884-5881)
- Paul L. A. M. Corstjens (ORCID: https://orcid.org/0000-0002-0004-0526)
- Jeroen Sijtsma (ORCID: https://orcid.org/0009-0006-4683-1995)
- Moses Egesa (ORCID: https://orcid.org/0000-0001-5136-868X)
- Maria Yazdanbakhsh (ORCID: https://orcid.org/0000-0002-7666-1441)
- Lisette van Lieshout (ORCID: https://orcid.org/0000-0001-8170-1172)
- Govert J. van Dam (ORCID: https://orcid.org/0000-0003-3773-0819)
- Harriet Mpairwe (ORCID: https://orcid.org/0000-0003-1199-4859)
- Marion König (ORCID: https://orcid.org/0000-0002-9892-218X)
- Sabine C.L. van Steenbergen
- Emma L. Houlder (ORCID: https://orcid.org/0000-0003-0448-6055)
- Eleni G. Iliopoulou
- Alison M. Elliott (ORCID: https://orcid.org/0000-0003-2818-9549)
- Friederike Sonnet (ORCID: https://orcid.org/0000-0003-0198-9917)
- Andrew S. MacDonald (ORCID: https://orcid.org/0000-0002-5356-1149)
- Emmanuella Driciru (ORCID: https://orcid.org/0000-0003-1146-1964)
- Yvonne C. M. Kruize
- Meta Roestenberg (ORCID: https://orcid.org/0000-0002-5052-2830)
- Stan T. Hilt (ORCID: https://orcid.org/0000-0002-4207-6850)
- Miriam Casacuberta-Partal (ORCID: https://orcid.org/0000-0001-5514-6996)
- Koen A. Stam (ORCID: https://orcid.org/0000-0003-0982-4439)
- Jan Pieter R. Koopman (ORCID: https://orcid.org/0000-0003-1335-9402)
- Laura de Bes-Roeleveld
Institutions
- Leiden University Medical Center (NL)
- University of Manchester (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Uganda Virus Research Institute (UG)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1038/s41467-025-62144-8
- Citations
- 4
- Primary Topic
- Parasites and Host Interactions
- Type
- article
- Field-Weighted Citation Impact
- 8.19
Funders
- London School of Hygiene and Tropical Medicine
- UK Research and Innovation
- European Commission
- Leids Universitair Medisch Centrum
- Foreign, Commonwealth and Development Office
- Medical Research Council
- European and Developing Countries Clinical Trials Partnership