Parasites trigger epithelial cell crosstalk to drive gut-brain signalling
Date
2026
Authors
Touhara, K.K.
Xu, J.
Castro, J.
Liang, H.-E.
Li, G.
Brizuela, M.
Harrington, A.M.
Garcia-Caraballo, S.
O'Donnell, T.
Neumann, D.
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Journal article
Citation
Nature, 2026; 1-32
Statement of Responsibility
Kouki K. Touhara, Jinhao Xu, Joel Castro, Hong-Erh Liang, Guochuan Li, Mariana Brizuela, Andrea M. Harrington, Sonia Garcia-Caraballo, Tracey O, Donnell, Daniel Neumann, Nathan D. Rossen, Fei Deng, Gudrun Schober, Yulong Li, Richard M. Locksley, Stuart M. Brierley, David Julius
Conference Name
Abstract
Parasitic infections modulate both immune and sensory responses, but how these systems collaborate to elicit protective behaviours remains incompletely understood. The gut epithelium contains specialized sensory cells that detect pathogens and irritants. These include cholinergic tuft cells, which sense parasites and initiate type 2 immune responses1,2,3, as well as serotonergic enterochromaffin (EC) cells, which detect irritants and communicate with afferent nerve fibres to transmit nociceptive signals4,5,6. Here we show that paracrine signalling between these cells constitutes a mechanism for neuro–immune interaction and gut–brain communication. We find that tuft cells use two distinct mechanisms of acetylcholine (ACh) release despite lacking synaptic vesicles and excitable membranes. These include acute release in response to parasite-derived metabolites, followed by constitutive ‘leak-like’ release, which occurs with type 2 inflammation. Although both mechanisms can activate muscarinic receptors on crypt-residing EC cells, only the sustained mode of ACh release elicits levels of serotonin sufficient to stimulate vagal afferent neurons that suppress food intake. This two-phase paracrine signalling mechanism explains how parasitic infection progresses from an initial asymptomatic phase to symptomatic established disease, in which type 2 immune and sensory signalling pathways within the gut–brain axis collaborate to evoke protective behaviours.
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©The author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.