Staphylococcal superantigen-like protein 13 activates neutrophils via formyl peptide receptor 2.

Yuxi Zhao,Kok P M Van Kessel,Carla J C De Haas,Malbert R C Rogers,Pieter-Jan A Haas,Jos A G Van Strijp

doi:10.1111/cmi.12941

Yuxi Zhao, Kok P M Van Kessel + Show 4 more

Open Access

https://doi.org/10.1111/cmi.12941

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Journal: Cellular Microbiology	Publication Date: Sep 17, 2018
Citations: 20	License type: cc-by

Affiliation: University Medical Center Utrecht

Abstract

Staphylococcal superantigen‐like (SSL) proteins, one of the major virulence factor families produced by Staphylococcus aureus, were previously demonstrated to be immune evasion molecules that interfere with a variety of innate immune defences. However, in contrast to characterised SSLs, which inhibit immune functions, we show that SSL13 is a strong activator of neutrophils via the formyl peptide receptor 2 (FPR2). Moreover, our data show that SSL13 acts as a chemoattractant and induces degranulation and oxidative burst in neutrophils. As with many other staphylococcal immune evasion proteins, SSL13 shows a high degree of human specificity. SSL13 is not able to efficiently activate mouse neutrophils, hampering in vivo experiments. In conclusion, SSL13 is a neutrophil chemoattractant and activator that acts via FPR2. Therefore, SSL13 is a unique SSL member that does not belong to the immune evasion class but is a pathogen alarming molecule. Our study provides a new concept of SSLs; SSLs not only inhibit host immune processes but also recruit human neutrophils to the site of infection. This new insight allows us to better understand complex interactions between host and S. aureus pathological processes.

Highlights

The Gram‐positive bacterium Staphylococcus aureus (S. aureus) is an opportunistic human pathogen that causes a wide range of diseases from mild skin infections to more serious life‐threatening wound and systemic infections (Spaan, Surewaard, Nijland, & van Strijp, 2013)
We found that an formyl peptide receptor 2 (FPR2) antagonist formyl peptide receptor‐like inhibitory protein (FLIPr) inhibited SSL13‐induced calcium mobilisation, as well as SSL13 binding to human neutrophils (Figure 3b,c)
Our data show that SSL13 induced a modest oxidative burst compared with the control FPR2 specific peptide WKYMVM (Figure 4c), but both SSL13‐ and WKYMVM‐induced oxidative burst in human neutrophils could be blocked by FLIPr (Figure 4c)

Summary

| INTRODUCTION

The Gram‐positive bacterium Staphylococcus aureus (S. aureus) is an opportunistic human pathogen that causes a wide range of diseases from mild skin infections to more serious life‐threatening wound and systemic infections (Spaan, Surewaard, Nijland, & van Strijp, 2013). Despite the functional differences and diversity in targets, the staphylococcal immune evasion proteins are secreted proteins that show remarkable resemblances These proteins contain very conserved structural properties (Jongerius et al, 2007). In contrast to the FPR1, the FPR2 is a promiscuous receptor with various unrelated ligands, which include peptides, parts of proteins, lipids, and small molecules, resulting in different intracellular responses in a ligand‐specific manner (Cattaneo, Parisi, & Ammendola, 2013) Another group of secreted proteins, of which many are involved in immune evasion, is the staphylococcal superantigen‐like (SSL) proteins (Thammavongsa et al, 2015). In contrast to many other immune evasion proteins that inhibit immune responses, we identified SSL13 as a chemoattractant and a neutrophil activator that acts via the FPR2

| RESULTS

| DISCUSSION

Findings

| Ethics statement