Intestinal NF-κB and STAT signalling is important for uptake and clearance in a Drosophila-Herpetomonas interaction model
| Autor: | Petros Ligoxygakis, Lihui Wang, Megan A. Sloan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cell signaling
Signal transduction chemistry.chemical_compound 0302 clinical medicine Animal Cells Gene expression Medicine and Health Sciences Drosophila Proteins Parasite hosting Protozoans 0303 health sciences Gene knockdown Stem Cells Drosophila Melanogaster Toll-Like Receptors Eukaryota Signaling cascades Animal Models 3. Good health Cell biology Intestines Insects STAT Transcription Factors STAT signaling Experimental Organism Systems Drosophila Anatomy Cellular Types Stem cell Drosophila melanogaster Research Article Trypanosoma Arthropoda lcsh:QH426-470 030231 tropical medicine Biology Research and Analysis Methods stat Host-Parasite Interactions 03 medical and health sciences Model Organisms Parasitic Diseases Animals Humans Progenitor cell Cell Proliferation 030304 developmental biology fungi Transcription Factor RelA Organisms Biology and Life Sciences NF-κB biology.organism_classification Invertebrates Parasitic Protozoans Gastrointestinal Tract lcsh:Genetics Enterocytes Fertility Gene Expression Regulation JAK-STAT signaling cascade chemistry Animal Studies Trypanosomatina Parasitic Intestinal Diseases Digestive System Transcription Factors |
| Zdroj: | PLoS Genetics, Vol 15, Iss 3, p e1007931 (2019) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | 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. Author summary Neglected Tropical Diseases are the most common diseases of the world’s poorest people. Many are caused by parasites called trypanosomatids that are transmitted to humans via insects belonging to the order of Diptera (also known as true flies). These flies (including tsetse, sand flies and black flies) are difficult to study in the lab and so the prospect of rapid progress in the basic biology of fly-parasite interaction is bleak. However, a model dipteran species with an extensive “tool-box” is the fruit fly Drosophila melanogaster with its natural trypanosomatid Herpetomonas muscarum. Here we establish the framework of their interaction with the view that part of this interaction will represent an evolutionary conserved component of the dipteran response to parasite infection and will inform more targeted studies into medically important but difficult to study Diptera. |
| Databáze: | OpenAIRE |
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