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Prodjinotho, U.F.* ; Gres, V.* ; Henkel, F. ; Lacorcia, M.* ; Dandl, R.* ; Haslbeck, M.* ; Schmidt, V.* ; Winkler, A.S.* ; Sikasunge, C.* ; Jakobsson, P.J.* ; Henneke, P.* ; Esser-von Bieren, J. ; Prazeres da Costa, C.U.*

Helminthic dehydrogenase drives PGE2 and IL-10 production in monocytes to potentiate Treg induction.

EMBO Rep. 23:e54096 (2022)

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Immunoregulation of inflammatory, infection-triggered processes in the brain constitutes a central mechanism to control devastating disease manifestations such as epilepsy. Observational studies implicate the viability of Taenia solium cysts as key factor determining severity of neurocysticercosis (NCC), the most common cause of epilepsy, especially in children, in Sub-Saharan Africa. Viable, in contrast to decaying, cysts mostly remain clinically silent by yet unknown mechanisms, potentially involving Tregs in controlling inflammation. Here, we show that glutamate dehydrogenase from viable cysts instructs tolerogenic monocytes to release IL-10 and the lipid mediator PGE2. These act in concert, converting naive CD4+ T cells into CD127−CD25hiFoxP3+CTLA-4+ Tregs, through the G protein-coupled receptors EP2 and EP4 and the IL-10 receptor. Moreover, while viable cyst products strongly upregulate IL-10 and PGE2 transcription in microglia, intravesicular fluid, released during cyst decay, induces pro-inflammatory microglia and TGF-β as potential drivers of epilepsy. Inhibition of PGE2 synthesis and IL-10 signaling prevents Treg induction by viable cyst products. Harnessing the PGE2-IL-10 axis and targeting TGF-ß signaling may offer an important therapeutic strategy in inflammatory epilepsy and NCC.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Glutamate Dehydrogenase ; Immune Regulation ; Prostaglandin E2 ; Taenia Solium Cyst ; Treg Cells

ISSN (print) / ISBN 1469-221X

e-ISSN 1469-3178

Journal EMBO Reports

Quellenangaben Volume: 23, Issue: 5, Article Number: e54096

Publisher EMBO Press

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Allergy Research (IAF)

Grants Open Access funding enabled and organized by Projekt DEAL
the DFG (Deutsche Forschungsgemeinschaft) (PH)
the Helmholtz Initiative and Networking Fund (JEvB)
the DFG (Deutsche Forschungsgemeinschaft) (FH, JEvB)
the DFG (Deutsche Forschungsgemeinschaft) (UFP, ML, CPdC)