The C-type lectin receptor MGL senses N-acetylgalactosamine on the unique Staphylococcus aureus ST395 wall teichoic acid.

Malgorzata E. Mnich,Astrid Hendriks,Rob Dalen,Jos A.G. Strijp,Guoqing Xia,Andreas Peschel,David Gerlach,Nina M. Sorge

doi:10.1111/cmi.13072

Abstract

Staphylococcus aureus is a common skin commensal but is also associated with various skin and soft tissue pathologies. Upon invasion, S. aureus is detected by resident innate immune cells through pattern‐recognition receptors (PRRs), although a comprehensive understanding of the specific molecular interactions is lacking. Recently, we demonstrated that the PRR langerin (CD207) on epidermal Langerhans cells senses the conserved β‐1,4‐linked N‐acetylglucosamine (GlcNAc) modification on S. aureus wall teichoic acid (WTA), thereby increasing skin inflammation. Interestingly, the S. aureus ST395 lineage as well as certain species of coagulase‐negative staphylococci (CoNS) produce a structurally different WTA molecule, consisting of poly‐glycerolphosphate with α‐O‐N‐acetylgalactosamine (GalNAc) residues, which are attached by the glycosyltransferase TagN. Here, we demonstrate that S. aureus ST395 strains interact with the human Macrophage galactose‐type lectin (MGL; CD301) receptor, which is expressed by dendritic cells and macrophages in the dermis. MGL bound S. aureus ST395 in a tagN‐ and GalNAc‐dependent manner but did not interact with different tagN‐positive CoNS species. However, heterologous expression of Staphylococcus lugdunensis tagN in S. aureus conferred phage infection and MGL binding, confirming the role of this CoNS enzyme as GalNAc‐transferase. Functionally, the detection of GalNAc on S. aureus ST395 WTA by human monocyte‐derived dendritic cells significantly enhanced cytokine production. Together, our findings highlight differential recognition of S. aureus glycoprofiles by specific human innate receptors, which may affect downstream adaptive immune responses and pathogen clearance.

Highlights

Staphylococcus aureus is a common member of the human microbiome and colonises up to 30% of the population, where it mostly resides in the nares and on the skin (Eriksen, Espersen, Rosdahl, & Jensen, 1995; Kluytmans, van Belkum, & Verbrugh, 1997; Wertheim et al, 2005)
We show the molecular interaction between wall teichoic acid (WTA) of S. aureus ST395 and macrophage galactose‐type lectin (MGL), an innate receptor of the C‐type lectin receptors (CLRs) family
This interaction is dependent on α‐GalNAc modifications of S. aureus WTA and contributes to increased cytokine production in MGL‐expressing monocyte‐ derived dendritic cells (moDCs)

Summary

| INTRODUCTION

Staphylococcus aureus is a common member of the human microbiome and colonises up to 30% of the population, where it mostly resides in the nares and on the skin (Eriksen, Espersen, Rosdahl, & Jensen, 1995; Kluytmans, van Belkum, & Verbrugh, 1997; Wertheim et al, 2005). In contrast to the common RboP‐GlcNAc WTA, S. aureus isolates of the ST395 lineage produce WTA composed of a poly‐glycerolphosphate (GroP) backbone decorated with α‐N‐acetyl‐D‐galactosamine (α‐ GalNAc) residues, which are attached by glycosyltransferase TagN (Winstel et al, 2013; Winstel, Sanchez‐Carballo, Holst, Xia, & Peschel, 2014) The synthesis of this structurally different WTA impacts recognition and horizontal gene transfer by phages (Winstel et al, 2013; Winstel et al, 2014). S. aureus ST395 does not interact with langerin (van Dalen et al, 2019) Both dermal dendritic cells (DCs) and dermal macrophages express the trimeric CLR macrophage galactose‐type lectin (MGL; CD301), which recognises terminal GalNAc residues as a result of a Gln‐Pro‐Asp motif in its CRD (Tanaka et al, 2017). Loss of tagN in S. aureus ST395 attenuates production of specific cytokines by human monocyte‐ derived dendritic cells (moDCs)

| RESULTS

| DISCUSSION

Findings

| EXPERIMENTAL PROCEDURES