T cell responses in repeated controlled human schistosome infection compared to natural exposure

Emmanuella Driciru, Jan Pieter R. Koopman, Sanne Steenbergen, Friederike Sonnet, Koen A. Stam, Laura de Bes-Roeleveld, Eva Iliopoulou, Jacqueline J. Janse, Jeroen Sijtsma, Irene Nambuya, Stan T. Hilt, Marion König, Yvonne Kruize, Miriam Casacuberta-Partal, Moses Egesa, Govert J. Dam, Paul L. A. M. Corstjens, Lisette Lieshout, Harriet Mpairwe, Andrew S. MacDonald, Maria Yazdanbakhsh, Alison M. Elliott, Meta Roestenberg and Emma L. Houlder ()
Additional contact information
Emmanuella Driciru: Leiden University Medical Center
Jan Pieter R. Koopman: Leiden University Medical Center
Sanne Steenbergen: Leiden University Medical Center
Friederike Sonnet: Leiden University Medical Center
Koen A. Stam: Leiden University Medical Center
Laura de Bes-Roeleveld: Leiden University Medical Center
Eva Iliopoulou: Leiden University Medical Center
Jacqueline J. Janse: Leiden University Medical Center
Jeroen Sijtsma: Leiden University Medical Center
Irene Nambuya: University of Manchester
Stan T. Hilt: Leiden University Medical Center
Marion König: Leiden University Medical Center
Yvonne Kruize: Leiden University Medical Center
Miriam Casacuberta-Partal: Leiden University Medical Center
Moses Egesa: Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit
Govert J. Dam: Leiden University Medical Center
Paul L. A. M. Corstjens: Leiden University Medical Center
Lisette Lieshout: Leiden University Medical Center
Harriet Mpairwe: Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit
Andrew S. MacDonald: University of Manchester
Maria Yazdanbakhsh: Leiden University Medical Center
Alison M. Elliott: Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit
Meta Roestenberg: Leiden University Medical Center
Emma L. Houlder: Leiden University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract 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+ 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+ 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.

Date: 2025
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DOI: 10.1038/s41467-025-62144-8

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