Toll signalling controls intestinal regeneration in <i>Drosophila</i>
The intestinal interphase is where epithelial renewal and tissue maintenance are balanced alongside immunological regulation. How these functions integrate with cellular signalling is under investigation. Here, we studied the role of the evolutionarily conserved innate immune Toll/NF-κB pathway in Drosophila intestinal regeneration. We found that the core components of the canonical Toll pathway were necessary for intestinal stem cell (ISC) mitosis in homeostasis and upon infection. Toll activation was sufficient to push ISCs into mitosis and the enteroblast (EB) fate, but blocked EB differentiation resulting in ISC and EB accumulation. This was mediated by JNK and Akt/TOR signalling. When JNKK, JNK, Akt or TOR activity was reduced in gut progenitors, ISC mitosis was suppressed. Toll activation also triggered suppression of antimicrobial lysozyme and amidase genes, which led to increased gut bacterial density. Our results identify Toll as necessary and sufficient for ISC mitosis. Our model is that the Toll pathway acts as a regulator of the intestinal landscape integrating JNK and Akt signals to achieve gut tissue renewal and control of commensal bacteria density.
Authors
- Filippos Stavropoulos (ORCID: https://orcid.org/0000-0002-4505-8164)
- Shivohum Bahuguna (ORCID: https://orcid.org/0000-0002-8294-0308)
- Chrysoula Pitsouli (ORCID: https://orcid.org/0000-0003-4074-9684)
- Guofan Peng (ORCID: https://orcid.org/0000-0001-8949-258X)
- Michael Boutros (ORCID: https://orcid.org/0000-0002-9458-817X)
- Yiorgos Apidianakis (ORCID: https://orcid.org/0000-0002-7465-3560)
- Aiswarya Udayakumar (ORCID: https://orcid.org/0000-0001-6342-0780)
- Petros Ligoxygakis (ORCID: https://orcid.org/0000-0002-9498-9993)
- Young Seok Lee (ORCID: https://orcid.org/0000-0002-5146-0037)
- Qi Xiao
- Jun Zhou
- Theodosia Hadjipanteli
- Caitlin MacClay
- Yuxian Xia
Institutions
- Chongqing Technology and Business University (CN)
- Chongqing University (CN)
- Hunan Normal University (CN)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University of Cyprus (CY)
- University of Oxford (GB)
- Chongqing University of Technology (CN)
- Heidelberg University (US)
Publication Details
- Journal
- Development
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1242/dev.204794
- Primary Topic
- Invertebrate Immune Response Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Cyprus
- University of Oxford
- National Natural Science Foundation of China
- Chongqing University
- Hunan Provincial Science and Technology Department
- Hunan University
- John Fell Fund, University of Oxford