Proceedings of The Physiological Society

Newcastle University (2009) Proc Physiol Soc 16, PC30

Poster Communications

Cell-specific immune and stress signalling in Drosophila malpighian tubules confer organismal survival

S. A. Davies1, L. Aitchison1, S. Terhzaz1, G. Overend1, S. Sebastian1, P. Cabrero1, J. A. Dow1,2

1. Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom. 2. College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.


The survival of organisms depends on their response to external stressors, such as infection, osmotic or ionic stress, or exposure to xenobiotics or toxins. As barriers between the external and internal environment, epithelia play key roles in defending against osmotic, oxidative and immune stress. Genetic and physiological studies in model organisms, such as Drosophila, have provided clear links between manipulation of stress-associated genes and physiological output, and for many purposes the available genetic tools for Drosophila make it a system of choice. As well as the whole-organism studies that have dominated stress research, powerful genetic tools provide the capability to drill down to specific cells or tissues. The Drosophila Malpighian tubule, analogous to vertebrate kidney and liver, is an epithelial model for cell-specific, organotypic ion transport and cell signalling studies; and for functional genomics and gene discovery. The tubule is a NO/cyclic cGMP (cGMP)-modulated fluid-transporting epithelium (1) critical for osmoregulatory and detoxifying functions (2,3). Our recent work has suggested that the Drosophila renal (Malpighian) tubule plays a key role in organismal defence against a wide range of stresses, not just osmotic. Tubules are immune tissues (4,5) which express anti-microbial peptides via the IMD (4) and Toll pathways (flyatlas.org). We show here that a tubule-specific cGMP-kinase (cGK) ‘switch’ modulates Nf-kB orthologue (Relish) activation, and IMD signalling in tubules. This cGK ‘switch’, targeted to only principal cells of the tubule, modulates survival of immune-challenged whole flies, providing the first evidence of cyclic nucleotide modulation of innate immunity. We have also shown that tubules are the first-line defence in bacteria-fed Drosophila and so are key ‘sentinels’ of immune challenge. Due to the high rates of metabolic activity in epithelia, they can be major sources of ROS in the organism, and thus must be equipped for stress sensing and responses. Tubules have specific adaptations to counter high mitochondrial activity and ROS production including enriched expression of ‘antioxidant’ genes including superoxide dismutase (SOD), mitochondrial SOD and catalase. We also show that the tubule is a key stress-sensing tissue for the whole organism, and that manipulation of specific genes in only tubule principal cells is sufficient to modulate organismal stress and immune responses. Using functional data, and data obtained from modelling gene networks, the integration of stress and immune signalling pathways in the tubule will be presented.

Where applicable, experiments conform with Society ethical requirements