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

Area of Science:

• Immunology
• Neuroscience
• Microbiology

Background:

• Formyl peptide receptors (Fpr) are innate immune chemoreceptors expressed by vomeronasal sensory neurons (VSNs) in the accessory olfactory system.
• The specific biological functions and coding mechanisms of these VSN-expressed Fpr receptors remain largely unknown.

Purpose of the Study:

• To investigate the function of mouse Fpr3 (Fpr-rs1) in recognizing bacterial peptides.
• To determine if Fpr3-mediated recognition of bacterial peptides elicits a behavioral response in mice.

Main Methods:

• Peptide synthesis and characterization of the f-MKKFRW motif.
• In vivo electrophysiology to record VSN activity in response to peptide exposure.
• Behavioral assays to assess innate avoidance responses in freely moving mice.
• Genetic analysis using Fpr3 knockout models.

Main Results:

• Mouse Fpr3 (Fpr-rs1) specifically recognizes the f-MKKFRW peptide motif found in the MgrB bacterial protein.
• MgrB peptide is produced and secreted by Enterobacteriaceae and selectively activates a subset of VSNs.
• Exposure to MgrB peptide stimulates VSNs and induces innate avoidance behavior in mice.
• Fpr3 is essential for the neuronal detection and subsequent avoidance of these bacterial peptides.

Conclusions:

• Fpr3 acts as a critical sensor for bacterial virulence-associated peptides.
• This study reveals a novel innate immune pathway involving VSNs and Fpr3 for detecting enteric bacterial threats.
• The findings highlight a link between bacterial virulence regulation and host innate avoidance behaviors.