The anthelmintic drug Praziquantel promotes human Tr1 differentiation

Autor: Patrick McCallum, Enwono Eyoh, Anne Astier, Justin Killick, Francisca Mutapi, Seth Amanfo
Přispěvatelé: Centre for Inflammation Research [Edinburgh, UK], Queen's Medical Researche Institute, University of Edinburgh-University of Edinburgh, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Eyoh, E, McCallum, P, Killick, J, Amanfo, S A, Mutapi, F & Astier, A 2019, ' The anthelmintic drug Praziquantel promotes human Tr1 differentiation ', Immunology and Cell Biology . https://doi.org/10.1111/imcb.12229
Immunology and Cell Biology
Immunology and Cell Biology, Nature Publishing Group, 2019, 97 (5), pp.512-518. ⟨10.1111/imcb.12229⟩
ISSN: 0818-9641
1440-1711
DOI: 10.1111/imcb.12229
Popis: Praziquantel (PZQ) is an anthelminthic human and veterinary drug used to treat trematode and cestode worms. Changes in immune responses have been demonstrated in humans following curative PZQ treatment of schistosome infections. These changes have been attributed to the removal of immunosupressive worms and immune responses to parasite antigens exposed from dying worms. To date, there has been no study investigating the potential direct effect of PZQ on the host immune cells. Herein, we analyzed the effect of PZQ on human CD4+ T cells classically costimulated by CD3/CD28 or costimulated by the complement regulator CD46 to induce Type 1 regulatory T cells (Tr1). Our results show that PZQ enhanced T cell proliferation, increased secretion of IL-17 and IL-10 but had no effect on secretion of GM-CSF or IFNγ. Moreover, PZQ increased the co-expression of CD49b and LAG-3, a hallmark of Tr1 cells, suggesting increased Tr1 differentiation. Indeed, supernatants from PZQ-treated cells were able to decrease bystander T cell activation, and this was partly reduced when blocking IL-10. Hence, our study demonstrates that PZQ directly modulates human T cell activation and promotes Tr1 differentiation, suggesting that PZQ may have immunomodulatory functions in parasite-unrelated human inflammatory diseases. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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