Bacterial MgrB peptide activates chemoreceptor Fpr3 in mouse accessory olfactory system and drives avoidance behaviour

Bernd Bufe,Martina Pyrski,Janina Eisenbeis,Peter Mombaerts,Yannick Teuchert,Trese Leinders-Zufall,Frank Zufall,Markus Bischoff,Günter Lochnit,Anabel Pérez-Gómez,Tomohiro Ishii,Andreas Schmid,Thomas Timm

doi:10.1038/s41467-019-12842-x

Abstract

Innate immune chemoreceptors of the formyl peptide receptor (Fpr) family are expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system. Their biological function and coding mechanisms remain unknown. We show that mouse Fpr3 (Fpr-rs1) recognizes the core peptide motif f-MKKFRW that is predominantly present in the signal sequence of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae. MgrB peptide can be produced and secreted by bacteria, and is selectively recognized by a subset of VSNs. Exposure to the peptide also stimulates VSNs in freely behaving mice and drives innate avoidance. Our data shows that Fpr3 is required for neuronal detection and avoidance of peptides derived from a conserved master virulence regulator of enteric bacteria.

Highlights

Innate immune chemoreceptors of the formyl peptide receptor (Fpr) family are expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system
We find that Fpr[3] functions as a pattern recognition receptor for a distinct subset of N-formyl methionine-containing peptides that are predominantly present in the signal sequence of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae
Our results are generally consistent with this hypothesis in that they show that the innate immune chemoreceptor Fpr[3] is required in the olfactory system to detect and avoid peptides that are predominantly present in signal sequences of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae

Summary

Introduction

Innate immune chemoreceptors of the formyl peptide receptor (Fpr) family are expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system. Subsets of mouse VSNs express several distinct immune-related molecules[22,23,24] including five Fprs[25,26,27,28,29] In analogy to their role in innate immunity, a chemosensory function associated with the identification of pathogens[26] or an assessment of the bacterial flora of conspecifics[25] has been hypothesised for vomeronasal Fprs as well. We find that Fpr[3] functions as a pattern recognition receptor for a distinct subset of N-formyl methionine-containing (fMet) peptides that are predominantly present in the signal sequence of the bacterial protein MgrB, a highly conserved regulator of virulence and antibiotic resistance in Enterobacteriaceae. 85% (334/392) of all database entries from bacterial MKKFRW-containing proteins represent virulence systems that promote the survival of bacterial cells within mammalian hosts[34,35,36,37]

Methods

Results

Conclusion