A variant on chromosome 2p13.3 is associated with atopic dermatitis in Chinese Han population

Cai, Xiaopan; Zheng, Xiaodong; Fang, Ling; Zhou, Fusheng; Sheng, Yujun; Wu, Yanyan; Yu, Chong-Xian; Jun, Zhu; Xiao, Feng‐Li

doi:10.1016/j.gene.2017.07.059

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…In addition, the inflammatory skin disorder atopic dermatitis (AD) is strongly associated with monocolonization by S. aureus, especially during inflammatory exacerbations [29,30]. Human genome-wide association studies identified the langerin-encoding gene Cd207 as an AD susceptibility locus [31,32] where certain single-nucleotide polymorphisms (SNPs) in an enhancer region of Cd207 were associated with a reduced risk of AD development. Detection of specific S. aureus signatures by langerin provides a possible functional link between langerin-expressing LCs and AD pathobiology.…”

Section: Host Receptors Interacting With S Aureus Wtamentioning

confidence: 99%

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Dalen

Peschel

Sorge

2020

Trends in Microbiology

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Staphylococcus aureus is a major opportunistic human pathogen that frequently causes disease in community and hospital settings. Nasal colonization is an important risk factor for developing invasive disease. Cell wall-associated glycopolymers called wall teichoic acids (WTAs) contribute to efficient nasal colonization by S. aureus. In addition, WTAs are key targets of the host immune system due to their accessibility and high abundance on the S. aureus cell surface. In this review we discuss the new insights into interactions between the host and S. aureus WTA and the implications of these interactions for preventative and therapeutic approaches against S. aureus-mediated disease.Teichoic Acids: At the Bacterium-Host Interface S. aureus is a Gram-positive opportunistic human pathogen that asymptomatically colonizes the nasopharynx of 20-30% of the human population. Nasal colonization is a risk factor for developing invasive infections, including pneumonia, osteomyelitis, endocarditis, and sepsis [1,2]. The teichoic acid (TA) glycopolymers (see Glossary) are major components of the Gram-positive bacterial cell wall, representing up to 60% of the total cell wall mass. TAs are either anchored in the plasma membrane as lipoteichoic acid (LTA), or covalently linked to peptidoglycan as wall teichoic acid (WTA). Both types of TA have crucial roles in cell growth, protection from environmental stress, and during colonization and infection of the host [3].TAs are key targets of the host immune system due to their exposure and high abundance on the S. aureus surface. In recent years, multiple molecular interactions between the human host and S. aureus TAs have been identified, of which the LTA-specific interactions are briefly summarized in Box 1. In this review we focus on the new insights into WTA-specific interactions of S. aureus with the human host. Importantly, we discuss the implications of these interactions for the development of preventative and therapeutic approaches against S. aureus. Structure of S. aureus WTAMany Gram-positive bacteria produce WTA, the structure of which can vary widely between species (Box 2). The majority of S. aureus lineages produce WTA that is comprised of up to 40 ribitolphosphate (RboP) subunits that are modified with D-alanine and N-acetylglucosamine (GlcNAc) residues (Figure 1A) [3], the biosynthesis of which is briefly summarized in Box 3. Importantly, the modifications of WTA functionalize the molecule, for instance by providing resistance to cationic antimicrobial peptides and antibiotics, mediating phage adsorption and facilitating colonization. Glycosylation of S. aureus RboP-WTAS. aureus RboP-WTA can be modified by three types of glycosylation, each requiring the activity of a dedicated glycosyltransferase that links a GlcNAc residue to the C3 or C4 RboP hydroxyl groups either in an αor β-configuration. This creates the following repertoire of GlcNAc modifications: α-1,4-GlcNAc catalyzed by TarM, β-1,4-GlcNAc catalyzed by TarS, and β-1,3-GlcNAc catalyzed by TarP (Figure 1A) [4...

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Section: Host Receptors Interacting With S Aureus Wtamentioning

confidence: 99%

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Dalen

Peschel

Sorge

2020

Trends in Microbiology

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“…How this relates to the involvement of LCs in human AD remains to be investigated. Second, genome-wide association studies (GWAS) identified CD207 , the gene encoding langerin, as an AD susceptibility locus (42, 43). In these studies, polymorphisms in a putative enhancer region of CD207 , which are predicted to increase langerin expression, were protective for AD.…”

Section: Discussionmentioning

confidence: 99%

Langerhans Cells Sense Staphylococcus aureus Wall Teichoic Acid through Langerin To Induce Inflammatory Responses

Dalen

Diaz

Rumpret

et al. 2019

mBio

100

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Staphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD [eczema]). Epicutaneous exposure to S. aureus induces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The molecular mechanisms underlying the interaction between S. aureus and LCs are poorly understood. Here we demonstrate that human LCs directly interact with S. aureus through the pattern recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with S. aureus through the conserved β-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating S. aureus from other staphylococcal species. Importantly, the specific S. aureus WTA glycoprofile strongly influences the level of proinflammatory cytokines that are produced by in vitro-generated LCs. Finally, in a murine epicutaneous infection model, S. aureus strongly upregulated transcripts of Cxcl1, Il6, and Il17, which required the presence of both human langerin and WTA β-GlcNAc. Our findings provide molecular insight into the unique proinflammatory capacities of S. aureus in relation to skin inflammation. IMPORTANCE The bacterium Staphylococcus aureus is an important cause of skin infections and is also associated with the occurrence and severity of eczema. Langerhans cells (LCs), a specific subset of skin immune cells, participate in the immune response to S. aureus, but it is yet unclear how LCs recognize S. aureus. Therefore, we investigated the molecular mechanism underlying the interaction between LCs and S. aureus. We identified that wall teichoic acid, an abundant polymer on the S. aureus surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate S. aureus from other related staphylococcal species and initiates a proinflammatory response similar to that observed in patients with eczema. Our data therefore provide important new insights into the relationship between S. aureus, LCs, and eczema.

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“…aureus is a driver of AD disease progression, which is mediated by LCs (Kobayashi et al, 2015). Interestingly, CD207, the gene encoding for langerin, was identified in genome-wide association studies as an AD susceptibility locus (Paternoster et al, 2015, Cai et al, 2017.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureuswall teichoic acid is a pathogen-associated molecular pattern that is recognized by langerin (CD207) on skin Langerhans cells

Diaz

Rumpret

et al. 2017

Preprint

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SummaryStaphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD). Langerhans cells (LCs) initiate a Th17 response upon exposure to S. aureus, which contributes to host defense but also to AD pathogenesis. However, the molecular mechanisms underlying the unique pro-inflammatory capacities of S. aureus remain unclear. We demonstrate that human LCs directly interact with S. aureus through the pattern-recognition receptor langerin (CD207), which specifically recognizes the conserved β-N-acetylglucosamine (GlcNAc) modifications of wall teichoic acid (WTA) that are not expressed by other staphylococcal species. The WTA glycoprofile strongly influences the production of Th1-and Th17-polarizing cytokines by LCs. Specifically, β-GlcNAc activates LCs, whereas co-decoration of WTA with α-GlcNAc through the enzyme TarM, uniformly present in the AD-associated CC1 lineage, attenuates LC immune activation. Our findings provide important mechanistic insights into the role of S. aureus in inflammatory skin disease.

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A variant on chromosome 2p13.3 is associated with atopic dermatitis in Chinese Han population

Cited by 9 publications

References 26 publications

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Wall Teichoic Acid in Staphylococcus aureus Host Interaction

Langerhans Cells Sense Staphylococcus aureus Wall Teichoic Acid through Langerin To Induce Inflammatory Responses

Staphylococcus aureuswall teichoic acid is a pathogen-associated molecular pattern that is recognized by langerin (CD207) on skin Langerhans cells

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