Intestinal NF-κB and STAT signalling is important for uptake and clearance in a Drosophila-Herpetomonas interaction model

Wang, L., Sloan, M. A. and Ligoxygakis, P. (2019) Intestinal NF-κB and STAT signalling is important for uptake and clearance in a Drosophila-Herpetomonas interaction model. PLoS Genetics, 15(3), e1007931. (doi: 10.1371/journal.pgen.1007931) (PMID:30822306) (PMCID:PMC6415867)

Abstract

Dipteran insects transmit serious diseases to humans, often in the form of trypanosomatid parasites. To accelerate research in more difficult contexts of dipteran-parasite relationships, we studied the interaction of the model dipteran Drosophila melanogaster and its natural trypanosomatid Herpetomonas muscarum. Parasite infection reduced fecundity but not lifespan in NF-κB/Relish-deficient flies. Gene expression analysis implicated the two NF-κB pathways Toll and Imd as well as STAT signalling. Tissue specific knock-down of key components of these pathways in enterocytes (ECs) and intestinal stem cells (ISCs) influenced initial numbers, infection dynamics and time of clearance. Herpetomonas triggered STAT activation and proliferation of ISCs. Loss of Relish suppressed ISCs, resulting in increased parasite numbers and delayed clearance. Conversely, overexpression of Relish increased ISCs and reduced uptake. Finally, loss of Toll signalling decreased EC numbers and enabled parasite persistence. This network of signalling may represent a general mechanism with which dipteran respond to trypanosomatids.

• Item Type: Articles
• Additional Information: Funding was provided by ERC Consolidator Grant (PL), BBSRC Project Grant (PL), and Wellcome Trust Doctoral Fellowship (MAS).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sloan, Dr Megan

Creator Roles

Sloan, M. A.: Investigation, Methodology, Writing – review and editing

• Authors: Wang, L., Sloan, M. A., and Ligoxygakis, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Genetics
• Publisher: Public Library of Science
• ISSN: 1553-7390
• ISSN (Online): 1553-7390
• Published Online: 01 March 2019
• Copyright Holders: Copyright © 2019 Wang et al.
• First Published: First published in PLoS Genetics 15(3): e1007931
• Publisher Policy: Reproduced under a Creative Commons License

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