Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophils
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Updated: Jul 3, 2026
Detecting Migration and Infiltration of Neutrophils in Mice
Published on: February 6, 2020
Erica L Southgate1, Rong L He, Ji-Liang Gao
1Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Abstract:
The prototypic formyl peptide N-formyl-Met-Leu-Phe (fMLF) is a major chemoattractant found in Escherichia coli culture supernatants and a potent agonist at human formyl peptide receptor (FPR) 1. Consistent with this, fMLF induces bactericidal functions in human neutrophils at nanomolar concentrations. However, it is a much less potent agonist for mouse FPR (mFPR) 1 and mouse neutrophils, requiring micromolar concentrations for cell activation. To determine whether other bacteria produce more potent agonists for mFPR1, we examined formyl peptides from Listeria monocytogenes and Staphylococcus aureus for their abilities to activate mouse neutrophils. A pentapeptide (N-formyl-Met-Ile-Val-Ile-Leu (fMIVIL)) from L. monocytogenes and a tetrapeptide (N-formyl-Met-Ile-Phe-Leu (fMIFL)) from S. aureus were found to induce mouse neutrophil chemotaxis at 1-10 nM and superoxide production at 10-100 nM, similar to the potency of fMLF on human neutrophils. Using transfected cell lines expressing mFPR1 and mFPR2, which are major forms of FPRs in mouse neutrophils, we found that mFPR1 is responsible for the high potency of fMIVIL and fMIFL. In comparison, activation of mFPR2 requires micromolar concentrations of the two peptides. Genetic deletion of mfpr1 resulted in abrogation of neutrophil superoxide production and degranulation in response to fMIVIL and fMIFL, further demonstrating that mFPR1 is the primary receptor for detection of these formyl peptides. In conclusion, the formyl peptides from L. monocytogenes and S. aureus are approximately 100-fold more potent than fMLF in activating mouse neutrophils. The ability of mFPR1 to detect bacterially derived formyl peptides indicates that this important host defense mechanism is conserved in mice.
Insights
Formyl peptides from Listeria monocytogenes and Staphylococcus aureus activate mouse neutrophils 100 times more potently than fMLF. Mouse formyl peptide receptor 1 (mFPR1) is key for detecting these bacterial chemoattractants, highlighting conserved host defense mechanisms.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- N-formyl-Met-Leu-Phe (fMLF) from E. coli is a potent chemoattractant for human neutrophils via formyl peptide receptor 1 (FPR1).
- fMLF shows significantly lower potency in activating mouse neutrophils, requiring micromolar concentrations.
- This suggests potential differences in bacterial chemoattractant recognition between humans and mice.
Purpose of the Study:
- To investigate if other bacteria produce more potent agonists for mouse formyl peptide receptor 1 (mFPR1).
- To identify the specific mouse formyl peptide receptors responsible for recognizing bacterial chemoattractants.
- To confirm the role of mFPR1 in mediating mouse neutrophil responses to bacterial formyl peptides.
Main Methods:
- Screening of formyl peptides from Listeria monocytogenes and Staphylococcus aureus for mouse neutrophil activation.
- Utilizing transfected cell lines expressing mouse FPR1 (mFPR1) and FPR2 (mFPR2) to assess receptor specificity.
- Employing genetic deletion of mfpr1 in mice to evaluate its necessity for neutrophil responses.
Main Results:
- A pentapeptide (fMIVIL) from L. monocytogenes and a tetrapeptide (fMIFL) from S. aureus potently activated mouse neutrophils at nanomolar concentrations.
- Mouse FPR1 (mFPR1) was identified as the primary receptor responsible for the high potency of fMIVIL and fMIFL.
- Genetic deletion of mfpr1 completely abrogated mouse neutrophil responses to these bacterial peptides, confirming mFPR1's critical role.
Conclusions:
- Formyl peptides from L. monocytogenes and S. aureus are significantly more potent agonists for mouse neutrophils than fMLF, acting via mFPR1.
- Mouse FPR1 (mFPR1) plays a crucial role in detecting bacterially derived formyl peptides.
- This study demonstrates a conserved mechanism of host defense against bacterial infections in mice, mediated by formyl peptide receptors.
