Mechanisms and consequence of bacteria detection by the Drosophila gut epithelium

Abstract

Since insect mostly developed on decaying matter and contaminated fruits, they are constantly ingesting bacteria. The insect model, Drosophila, is therefore well adapted to study the interactions that take place between the gut epithelia and either resident or infectious bacteria. In order to provide an ad hoc immune response, gut epithelial cells must detect the presence of bacteria. In a recent report, Bosco-Drayon et al. identify the main receptors by which Drosophila sense gut associated bacteria and analyze how this bacteria-receptor interaction translate into gene activation.

Keywords: NF-kB; PGRP; drosophila; gut epithelia; microbiota; peptidoglycan.

Figure 1. Model for bacteria detection by the Drosophila midgut. Ingested bacteria pass through the foregut (pharynx and esophagus) and reach the midgut that is made of four domains from anterior to posterior, the proventriculus, the ventriculus, the Copper cells region and posterior midgut. Bacteria are concentrated in the anterior domains but are able to release PGN fragments that can reach more posterior regions. It is unclear whether cell wall PGN or PGN released by bacteria are detected by the same mechanisms in the gut. One could imagine that one is detected by PGRP-LC while the other is a PGRP-LE ligand. The immune response in the proventriculus is fully PGRP-LC dependent and antagonized by PGRP-LE. It mainly consists of the production of antimicrobial peptides and is thought to regulate bacterial entry into the gut lumen. In the ventriculus, both PGRP-LE and –LC are required for IMD pathway activation. The more posterior domains that are devoid of bacteria are PGRP-LE dependent as far as IMD pathway activation is concerned. Activation of the NFkB pathway in these domains mainly leads to the production of IMD pathway negative regulators that by dampening the signaling protect the host from excessive immune response and prevent spreading of the immune response to remote tissues such as the fat body. This is a simplified model as AMP and INR are produced in all domains but at different levels. Some unanswered questions remain: (1) How does PGN reach or activate intracellular PGRP-LE? (2) How does PGRP-LE antagonize IMD pathway? (3) Why are both PGRP-LC and –LE required to activate IMD signaling in the ventriculus? (4) Why are AMPs mainly produced in anterior domains and INR in posterior domains? Does PGRP-LC and PGRP-LE activation lead to same transcriptional output?