The Journal of Infectious Diseases. 208(1):159–169, JUL 2013
DOI: 10.1093/infdis/jis524
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PMID: 23045617
Issn Print: 0022-1899
Publication Date: 2013/07/01
Integrated Analysis of Innate, Th1, Th2, Th17, and Regulatory Cytokines Identifies Changes in Immune Polarisation Following Treatment of Human Schistosomiasis
Claire Bourke;Norman Nausch;Nadine Rujeni;Laura Appleby;Kate Mitchell;Nicholas Midzi;Takafira Mduluza;Francisca Mutapi;
+ Author Information
1Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, United Kingdom2National Institute of Health Research, Harare, Zimbabwe3Biochemistry Department, University of Zimbabwe, Harare
Abstract
Background. Schistosomiasis elicits cross-regulatory immune responses, but it is unclear how antihelminthic treatment affects this balance. This study integrates data on 13 cytokines elicited by 3 schistosome to examine how praziquantel treatment alters immune polarization and whether post-treatment cytokine profiles influence reinfection status.Methods. Venous blood from 72 Schistosoma haematobium–exposed participants was cultured with schistosome egg, adult worm, and cercaria antigens pre– and 6 weeks post–praziquantel treatment. Innate inflammatory (tumor necrosis factor α [TNF-α], interleukin(IL-)-6, IL-8), Th1 (interferon γ [IFN-γ], IL-2, IL-12p70), Th2 (IL-4, IL-5, IL-13), Th17 (IL-17A, IL-21, IL-23p19), and regulatory (IL-10) cytokines were quantified via enzyme-linked immunosorbent assay. Cytokine data was integrated using nonmetric multidimensional scaling and factor analysis.Results. Egg-specific cytokine phenotypes became more proinflammatory post-treatment due to increased TNF-α, IL-6, IL-8, IFN-γ, IL-12p70, and IL-23 levels. Post-treatment cercariae-specific responses were also more proinflammatory reflecting elevated IL-8. In contrast, post-treatment adult worm-specific responses were less inflammatory, reflecting lower post-treatment IL-6. A combination of egg-induced IL-6, IL-12p70, IL-21, and IL-23 and adult worm-induced IL-5 and IL-21 post-treatment was associated with reduced reinfection risk 18 months later.Conclusions. Praziquantel treatment markedly alters polarization of schistosome-specific cytokine responses, and these changes, particularly in response to egg-stage parasites, may promote resistance to reinfection.
