Peptidoglycan induces loss of a nuclear peptidoglycan recognition protein during host tissue development in a beneficial animal-bacterial symbiosis

Abstract

SummaryPeptidoglycan recognition proteins (PGRPs) are mediators of innate immunity and recently have been implicated in developmental regulation. To explore the interplay between these two roles, we characterized a PGRP in the host squid Euprymna scolopes (EsPGRP1) during colonization by the mutualistic bacterium Vibrio fischeri. Previous research on the squid-vibrio symbiosis had shown that, upon colonization of deep epithelium-lined crypts of the host light organ, symbiont-derived peptidoglycan monomers induce apoptosismediated regression of remote epithelial fields involved in the inoculation process. In this study, immunofluorescence microscopy revealed that EsPGRP1 localizes to the nuclei of epithelial cells, and symbiont colonization induces the loss of EsPGRP1 from apoptotic nuclei. The loss of nuclear EsPGRP1 occurred prior to DNA cleavage and breakdown of the nuclear membrane, but followed chromatin condensation, suggesting that it occurs during late-stage apoptosis. Experiments with purified peptidoglycan monomers and with V. fischeri mutants defective in peptidoglycan-monomer release provided evidence that these molecules trigger nuclear loss of EsPGRP1 and apoptosis. The demonstration of a nuclear PGRP is unprecedented, and the dynamics of EsPGRP1 during apoptosis provide a striking example of a connection between microbial recognition and developmental responses in the establishment of symbiosis.

The chemistry of negotiation: Rhythmic, glycan-driven acidification in a symbiotic conversation

“…The squid encodes homologs of zebrafish enzymes that inactivate immunogenic microbe-associated molecular pattern (MAMP) molecules. These enzymes lose activity at a low pH (48)(49)(50)(51), suggesting that diel tissue acidification might lead to a local or systemic increase in MAMP levels at night. MAMPs promote the establishment of symbiosis by signaling pattern recognition receptors (PRRs) (8); thus, it is possible that acidification underlies a daily activation of PRR signal cascades.…”

“…Chitin was detected in hemocytes and light-organ tissues, using commercially available FITC-or TRITCconjugated CBP (New England Biolabs) (22). Light-organ tissues and hemocytes from the hemolymph of >4-wk-old squid, or whole tissue from 2-d-old light organs, were collected and prepared for immunocytochemistry (ICC) and confocal microscopy, using standard procedures (22,48).…”

Neisseria gonorrhoeae Crippled Its Peptidoglycan Fragment Permease To Facilitate Toxic Peptidoglycan Monomer Release

“…Nonetheless, the release of PG monomers by bacteria tends to lead to inflammation and the death of animal host cells, whether or not this interaction leads to beneficial or detrimental effects at the organismal level. Tetrapeptide monomer (also known as TCT) and lipopolysaccharide released by Vibrio fischeri work synergistically to induce the regression of ciliated epithelial cells near the light organ of the Hawaiian bobtail squid to allow the establishment of squid-Vibrio symbiosis (21,50,51). The production of PG fragments is also thought to be important for the pathogenesis of multiple bacterial species, including but not limited to human pathogens such as Helicobacter pylori and Shigella flexneri, as well as plant pathogens such as Pseudomonas syringae and Erwinia amylovora (reviewed in reference 48).…”

PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse’s offspring

“…The Drosophila PGRP-LB has a catalytic amidase activity that can degrade PGN and prevent host immune activation (16,17). The ability of PGRP-LB to control host immune activation provides protection to beneficial microbes in several insects (18)(19)(20). In tsetse, pgrp-lb is expressed in Wigglesworthia harboring tissues (bacteriome and milk gland), and there is a positive correlation between Wigglesworthia density and pgrp-lb expression levels.…”