Intestinal inflammation and stem cell homeostasis in aging Drosophila melanogaster - PubMed (original) (raw)

Review

Intestinal inflammation and stem cell homeostasis in aging Drosophila melanogaster

Arshad Ayyaz et al. Front Cell Infect Microbiol. 2013.

Abstract

As a barrier epithelium, the intestinal epithelium has to coordinate physiological functions like digestion and nutrient resorption with the control of commensal bacteria and the prevention of pathogenic infections. It can therefore mount powerful innate immune and inflammatory responses, while, at the same time, maintaining tissue homeostasis through regenerative processes. How these different functions are coordinated remains unclear, and further insight is required to understand the age-related loss of homeostasis in this system, as well as the etiology of inflammatory and proliferative diseases of the gut. Recent work in Drosophila melanogaster has provided important new insight into the regulation of regenerative activity, innate immune homeostasis, commensal control, as well as age-related dysfunction in the intestine. Interestingly, many of the identified processes and mechanisms mirror similar homeostatic processes in the vertebrate intestine. This review summarized the current understanding of how innate immune responses, changes in commensal bacteria, and other challenges influence regenerative activity in the aging intestinal epithelium of flies and draws parallels to similar processes in mammals.

Keywords: aging; dysbiosis; dysplasia; stem cell; tissue homeostasis.

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Figures

Figure 1

Figure 1

The Drosophila intestine. The midgut in Drosophila is subdivided into anterior midgut (AM), middle midgut (MM) and posterior midgut (PM) regions. It contains single population of mitotically active intestinal stem cells (ISCs), which spread throughout from anterior to posterior regions. An ISC asymmetrically divides to generate an intermediate enteroblast (EB), which eventually differentiates either into an enterocyte (EC) or enteroendocrine (EE) cell. proventriculous (PV), hindgut (HG), Malpighian tubules (MT), peritrophic matrix (PM).

Figure 2

Figure 2

Mechanism of intestinal dysplasia. Under normal homeostatic conditions, activity of Immune deficiency (IMD) pathway is tightly regulated by multiple factors. This ensures moderate innate immune response sufficient to keep intestinal microbes in check while preventing excessive immune activation. In an aging intestine, however, loss of these regulatory mechanisms leads to chronic inflammation and dysbiosis, which results in dysplasia and disruption of tissue homeostasis. Dual oxidase (Duox), reactive oxygen species (ROS), peptidoglycan (PGRP), Relish (Rel), poor Imd response upon knock-in (PIRK), antimicrobial peptides (AMP).

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