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Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila
- Source :
- PLoS Genetics, Vol 12, Iss 5, p e1006089 (2016), PLoS Genetics
- Publication Year :
- 2016
- Publisher :
- Public Library of Science (PLoS), 2016.
-
Abstract
- The JAK/STAT pathway is a key signaling pathway in the regulation of development and immunity in metazoans. In contrast to the multiple combinatorial JAK/STAT pathways in mammals, only one canonical JAK/STAT pathway exists in Drosophila. It is activated by three secreted proteins of the Unpaired family (Upd): Upd1, Upd2 and Upd3. Although many studies have established a link between JAK/STAT activation and tissue damage, the mode of activation and the precise function of this pathway in the Drosophila systemic immune response remain unclear. In this study, we used mutations in upd2 and upd3 to investigate the role of the JAK/STAT pathway in the systemic immune response. Our study shows that haemocytes express the three upd genes and that injury markedly induces the expression of upd3 by the JNK pathway in haemocytes, which in turn activates the JAK/STAT pathway in the fat body and the gut. Surprisingly, release of Upd3 from haemocytes upon injury can remotely stimulate stem cell proliferation and the expression of Drosomycin-like genes in the intestine. Our results also suggest that a certain level of intestinal epithelium renewal is required for optimal survival to septic injury. While haemocyte-derived Upd promotes intestinal stem cell activation and survival upon septic injury, haemocytes are dispensable for epithelium renewal upon oral bacterial infection. Our study also indicates that intestinal epithelium renewal is sensitive to insults from both the lumen and the haemocoel. It also reveals that release of Upds by haemocytes coordinates the wound-healing program in multiple tissues, including the gut, an organ whose integrity is critical to fly survival.<br />Author Summary Innate immunity acts as the primary line of defense to overcome invading organisms. This response starts through sensing of microbe-specific molecules such as lipopolysaccharide and peptidoglycan by host receptors. Metazoans can also recognize signals that are associated with tissue damage and wounding, to then activate specific pathways involved in tissue repair or inflammation. Previous studies have suggested a link between JAK/STAT activation and tissue repair in Drosophila, but the mode of activation and the precise function of this pathway remain unclear. In this article, we analyze the role of the JAK/STAT pathway in the resistance to wounding in Drosophila. We show that this pathway contributes to fly resistance to wounding and bacterial infection. Mechanistically, injury induces the production of secreted molecules called Unpaireds by blood cells, which then activate the JAK/STAT pathway in the fat body (an organ equivalent to the vertebrate liver) and in the gut. One of the most surprising findings of our study is that Unpaireds released from blood cells can remotely stimulate intestinal stem cell proliferation. Thus, we uncover an unexpected interaction between circulating blood cells and intestinal stem cell proliferation that contributes to fly survival after injury.
- Subjects :
- Bacterial Diseases
0301 basic medicine
Cell signaling
Cancer Research
Hemocytes
Fat Body
Signal transduction
Pathology and Laboratory Medicine
Biochemistry
Epithelium
Fats
0302 clinical medicine
Intestinal mucosa
Animal Cells
Medicine and Health Sciences
Drosophila Proteins
Intestinal Mucosa
Genetics (clinical)
Mammals
Drosophila Melanogaster
Stem Cells
Signaling cascades
JAK-STAT signaling pathway
Animal Models
Lipids
Intestinal epithelium
c-Jun N-terminal kinase signaling cascade
Bacterial Pathogens
Cell biology
Insects
Intestines
STAT Transcription Factors
Infectious Diseases
Medical Microbiology
Drosophila
Anatomy
Cellular Types
Pathogens
Stem cell
Research Article
Arthropoda
lcsh:QH426-470
Enterococcus Faecalis
Biology
Research and Analysis Methods
Microbiology
stat
03 medical and health sciences
Model Organisms
Genetics
Animals
Microbial Pathogens
Molecular Biology
Transcription factor
Ecology, Evolution, Behavior and Systematics
Janus Kinases
Bacteria
Organisms
Biology and Life Sciences
Invertebrates
Immunity, Innate
Gastrointestinal Tract
lcsh:Genetics
Biological Tissue
030104 developmental biology
Gene Expression Regulation
Immunology
Janus kinase
Digestive System
Enterococcus
030217 neurology & neurosurgery
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 12
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....a4de58c9d2437096b8db35cca35d3f58