PMID- 20949035
OWN - NLM
STAT- MEDLINE
DCOM- 20110307
LR  - 20240316
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 10
DP  - 2010 Oct 7
TI  - Staphylococcal peptidoglycan co-localizes with Nod2 and TLR2 and activates innate 
      immune response via both receptors in primary murine keratinocytes.
PG  - e13153
LID - e13153 [pii]
LID - 10.1371/journal.pone.0013153 [doi]
AB  - In mammalian host cells staphylococcal peptidoglycan (PGN) is recognized by Nod2. 
      Whether PGN is also recognized by TLR2 is disputed. Here we carried out PGN 
      co-localization and stimulation studies with TLR2 and Nod2 in wild type and 
      mutant host cells. To exclude contamination with lipoproteins, polymeric 
      staphylococcal PGN (PGN(pol)) was isolated from Staphylococcus aureus Deltalgt 
      (lacking lipidated prelipoproteins). PGN(pol) was biotinylated (PGN-Bio) for 
      fluorescence monitoring with specific antibodies. Keratinocytes from murine oral 
      epithelium (MK) readily internalized PGN-Bio in an endocytosis-like process. In 
      wt MK, PGN(pol) induced intracellular accumulation of Nod2 and TLR2 and 
      co-localized with Nod2 and TLR2, but not with TLR4. In TLR2-deficient MK Nod2 and 
      in Nod2-deficient MK TLR2 was induced, indicating that PGN(pol) recognition by 
      Nod2 is independent of TLR2 and vice versa. In both mutants IL-6 and IL-1B 
      release was decreased by approximately 50% compared to wt MK, suggesting that the 
      immune responses induced by Nod2 and TLR2 are comparable and that the two 
      receptors act additively in MK. In TLR2-transfected HEK293 cells PGN(pol) induced 
      NFkB-promoter fused luciferase expression. To support the data, co-localization 
      and signaling studies were carried out with SHL-PGN, a lipase protein covalently 
      tethered to PGN-fragments of varying sizes at its C-terminus. SHL-PGN also 
      co-localized with Nod2 or TLR2 and induced their accumulation, while SHL without 
      PGN did not. The results show that staphylococcal PGN not only co-localizes with 
      Nod2 but also with TLR2. PGN is able to stimulate the immune system via both 
      receptors.
FAU - Muller-Anstett, Maria Anna
AU  - Muller-Anstett MA
AD  - Microbial Genetics, University of Tubingen, Tubingen, Germany.
FAU - Muller, Patrick
AU  - Muller P
FAU - Albrecht, Till
AU  - Albrecht T
FAU - Nega, Mulugeta
AU  - Nega M
FAU - Wagener, Jeanette
AU  - Wagener J
FAU - Gao, Qiang
AU  - Gao Q
FAU - Kaesler, Susanne
AU  - Kaesler S
FAU - Schaller, Martin
AU  - Schaller M
FAU - Biedermann, Tilo
AU  - Biedermann T
FAU - Gotz, Friedrich
AU  - Gotz F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101007
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (NF-kappa B)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Nod2 protein, mouse)
RN  - 0 (Peptidoglycan)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 6SO6U10H04 (Biotin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biotin/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Endocytosis
MH  - *Immunity, Innate
MH  - Keratinocytes/cytology/*immunology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mouth Mucosa/immunology/metabolism
MH  - NF-kappa B/metabolism
MH  - Nod2 Signaling Adaptor Protein/*metabolism
MH  - Peptidoglycan/*metabolism
MH  - Spectrometry, Fluorescence
MH  - Staphylococcus aureus/*metabolism
MH  - Toll-Like Receptor 2/*metabolism
PMC - PMC2951902
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/10/16 06:00
MHDA- 2011/03/08 06:00
PMCR- 2010/10/07
CRDT- 2010/10/16 06:00
PHST- 2010/06/30 00:00 [received]
PHST- 2010/08/24 00:00 [accepted]
PHST- 2010/10/16 06:00 [entrez]
PHST- 2010/10/16 06:00 [pubmed]
PHST- 2011/03/08 06:00 [medline]
PHST- 2010/10/07 00:00 [pmc-release]
AID - e13153 [pii]
AID - 10-PONE-RA-20664R1 [pii]
AID - 10.1371/journal.pone.0013153 [doi]
PST - epublish
SO  - PLoS One. 2010 Oct 7;5(10):e13153. doi: 10.1371/journal.pone.0013153.