PMID- 33591717
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20210623
IS  - 2373-8227 (Electronic)
IS  - 2373-8227 (Linking)
VI  - 7
IP  - 3
DP  - 2021 Mar 12
TI  - Impact of Glycan Linkage to Staphylococcus aureus Wall Teichoic Acid on Langerin 
      Recognition and Langerhans Cell Activation.
PG  - 624-635
LID - 10.1021/acsinfecdis.0c00822 [doi]
AB  - Staphylococcus aureus is the leading cause of skin and soft tissue infections. It 
      remains incompletely understood how skin-resident immune cells respond to 
      invading S. aureus and contribute to an effective immune response. Langerhans 
      cells (LCs), the only professional antigen-presenting cell type in the epidermis, 
      sense S. aureus through their pattern-recognition receptor langerin, triggering a 
      proinflammatory response. Langerin recognizes the beta-1,4-linked 
      N-acetylglucosamine (beta1,4-GlcNAc) but not alpha-1,4-linked GlcNAc (alpha1,4-GlcNAc) 
      modifications, which are added by dedicated glycosyltransferases TarS and TarM, 
      respectively, on the cell wall glycopolymer wall teichoic acid (WTA). Recently, 
      an alternative WTA glycosyltransferase, TarP, was identified, which also modifies 
      WTA with beta-GlcNAc but at the C-3 position (beta1,3-GlcNAc) of the WTA ribitol 
      phosphate (RboP) subunit. Here, we aimed to unravel the impact of beta-GlcNAc 
      linkage position for langerin binding and LC activation. Using genetically 
      modified S. aureus strains, we observed that langerin similarly recognized 
      bacteria that produce either TarS- or TarP-modified WTA, yet tarP-expressing S. 
      aureus induced increased cytokine production and maturation of in vitro-generated 
      LCs compared to tarS-expressing S. aureus. Chemically synthesized WTA molecules, 
      representative of the different S. aureus WTA glycosylation patterns, were used 
      to identify langerin-WTA binding requirements. We established that beta-GlcNAc is 
      sufficient to confer langerin binding, thereby presenting synthetic WTA molecules 
      as a novel glycobiology tool for structure-binding studies and for elucidating S. 
      aureus molecular pathogenesis. Overall, our data suggest that LCs are able to 
      sense all beta-GlcNAc-WTA producing S. aureus strains, likely performing an 
      important role as first responders upon S. aureus skin invasion.
FAU - Hendriks, Astrid
AU  - Hendriks A
AD  - Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 
      CX Utrecht, The Netherlands.
AD  - Glaxo-Smith Kline, 53100 Siena, Italy.
FAU - van Dalen, Rob
AU  - van Dalen R
AD  - Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 
      CX Utrecht, The Netherlands.
FAU - Ali, Sara
AU  - Ali S
AD  - Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The 
      Netherlands.
FAU - Gerlach, David
AU  - Gerlach D
AD  - Interfaculty Institute of Microbiology and Infection Medicine, University of 
      Tubingen, 72074 Tubingen, Germany.
AD  - Partner Site Tubingen, German Centre for Infection Research (DZIF), 72074 
      Tubingen, Germany.
FAU - van der Marel, Gijsbert A
AU  - van der Marel GA
AD  - Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The 
      Netherlands.
FAU - Fuchsberger, Felix F
AU  - Fuchsberger FF
FAU - Aerts, Piet C
AU  - Aerts PC
AD  - Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 
      CX Utrecht, The Netherlands.
FAU - de Haas, Carla J C
AU  - de Haas CJC
AD  - Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 
      CX Utrecht, The Netherlands.
FAU - Peschel, Andreas
AU  - Peschel A
AD  - Interfaculty Institute of Microbiology and Infection Medicine, University of 
      Tubingen, 72074 Tubingen, Germany.
AD  - Partner Site Tubingen, German Centre for Infection Research (DZIF), 72074 
      Tubingen, Germany.
FAU - Rademacher, Christoph
AU  - Rademacher C
AUID- ORCID: 0000-0001-7082-7239
FAU - van Strijp, Jos A G
AU  - van Strijp JAG
AD  - Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 
      CX Utrecht, The Netherlands.
FAU - Codee, Jeroen D C
AU  - Codee JDC
AUID- ORCID: 0000-0003-3531-2138
AD  - Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The 
      Netherlands.
FAU - van Sorge, Nina M
AU  - van Sorge NM
AUID- ORCID: 0000-0002-2695-5863
AD  - Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584 
      CX Utrecht, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210216
PL  - United States
TA  - ACS Infect Dis
JT  - ACS infectious diseases
JID - 101654580
RN  - 0 (Polysaccharides)
RN  - 0 (Teichoic Acids)
SB  - IM
MH  - Humans
MH  - Langerhans Cells
MH  - Polysaccharides
MH  - *Staphylococcal Infections
MH  - *Staphylococcus aureus/genetics
MH  - Teichoic Acids
PMC - PMC8023653
OTO - NOTNLM
OT  - Langerhans cell
OT  - Staphylococcus aureus
OT  - glycosylation
OT  - langerin
OT  - pattern-recognition receptor
OT  - wall teichoic acid
COIS- The authors declare no competing financial interest.
EDAT- 2021/02/17 06:00
MHDA- 2021/06/24 06:00
PMCR- 2021/04/06
CRDT- 2021/02/16 17:08
PHST- 2021/02/17 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2021/02/16 17:08 [entrez]
PHST- 2021/04/06 00:00 [pmc-release]
AID - 10.1021/acsinfecdis.0c00822 [doi]
PST - ppublish
SO  - ACS Infect Dis. 2021 Mar 12;7(3):624-635. doi: 10.1021/acsinfecdis.0c00822. Epub 
      2021 Feb 16.