Commensal microbiota-induced redox signaling activates proliferative signals in the intestinal stem cell microenvironment

• Type of Material: Article
• Authors: April R. Reedy, Emory University; Liping Luo, Emory University; Andrew Neish, Emory University; Rheinallt Jones, Emory University
• Language: English
• Date: 2019-02-01
• Publisher: The Company of Biologists Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © 2019. Published by The Company of Biologists Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1242/dev.171520
• Title of Journal or Parent Work: Development
• Volume: 146
• Issue: 3
• Grant/Funding Information: The Bloomington Drosophila Stock Center is supported by the National Institutes of Health (P40OD018537).; R.M.J. is supported in part by the National Institutes of Health grant R01DK098391.; A.R.R. is funded by the T32DK007771-06 training grant. Deposited in PMC for release after 12 months.; A.S.N. is supported, in part, by the National Institutes of Health grants R01DK071604 and RO1AI064462.
• Keywords: ROS; Science & Technology; Developmental Biology; Non-cell autonomous; JAK/STAT; Life Sciences & Biomedicine; Nrf2; Stem cell; NRF2; Drosophila; Homeostasis; Glutathione; Generation
• Research Categories: Health Sciences, Pathology; Biology, Microbiology; Biology, Cell

Abstract

A distinct taxon of the Drosophila microbiota, Lactobacillus plantarum, is capable of stimulating the generation of reactive oxygen species (ROS) within cells, and inducing epithelial cell proliferation. Here, we show that microbial-induced ROS generation within Drosophila larval stem cell compartments exhibits a distinct spatial distribution. Lactobacilli-induced ROS is strictly excluded from defined midgut compartments that harbor adultmidgut progenitor (AMP) cells, forming a functional ‘ROS sheltered zone’ (RSZ). The RSZ is undiscernible in germ-free larvae, but forms following monocolonization with L. plantarum. L. plantarum is a strong activator of the ROS-sensitive CncC/Nrf2 signaling pathway within enterocytes. Enterocyte-specific activation of CncC stimulated the proliferation of AMPs, which demonstrates that pro-proliferative signals are transduced from enterocytes to AMPs. Mechanistically, we show that the cytokine Upd2 is expressed in the gut following L. plantarum colonization in a CncC-dependent fashion, and may function in lactobacilli-induced AMP proliferation and intestinal tissue growth and development.