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Vigilant Keratinocytes Trigger PAMP Signaling in Response to Streptococcal M1 Protein.

Persson, Sandra LU ; Wilk, Laura LU ; Mörgelin, Matthias LU and Herwald, Heiko LU (2015) In Infection and Immunity 83(12). p.4673-4681
Abstract
The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a PAMP to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of mitogen-activated kinases, ERK, p38 and JNK, and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of... (More)
The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a PAMP to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of mitogen-activated kinases, ERK, p38 and JNK, and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of inflammatory mediators released, such as IL-8, GROα, MIF, EMMPRIN, IL-1α, IL-1Ra, and ST2 in response to streptococcal M1 protein. The expression of IL-8 is dependent on TLR2 activity and subsequent activation of the MAP kinases ERK and p38. Notably this signaling seems distinct for IL-8 release and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate pro-inflammatory in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
83
issue
12
pages
4673 - 4681
publisher
American Society for Microbiology
external identifiers
  • pmid:26416902
  • wos:000364944400021
  • scopus:84949658521
ISSN
1098-5522
DOI
10.1128/IAI.00887-15
language
English
LU publication?
yes
id
c26e5828-15c0-4929-9352-53316142b3c0 (old id 8034573)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26416902?dopt=Abstract
date added to LUP
2015-10-03 13:00:42
date last changed
2017-11-19 03:04:08
@article{c26e5828-15c0-4929-9352-53316142b3c0,
  abstract     = {The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a PAMP to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of mitogen-activated kinases, ERK, p38 and JNK, and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of inflammatory mediators released, such as IL-8, GROα, MIF, EMMPRIN, IL-1α, IL-1Ra, and ST2 in response to streptococcal M1 protein. The expression of IL-8 is dependent on TLR2 activity and subsequent activation of the MAP kinases ERK and p38. Notably this signaling seems distinct for IL-8 release and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate pro-inflammatory in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein.},
  author       = {Persson, Sandra and Wilk, Laura and Mörgelin, Matthias and Herwald, Heiko},
  issn         = {1098-5522},
  language     = {eng},
  number       = {12},
  pages        = {4673--4681},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Vigilant Keratinocytes Trigger PAMP Signaling in Response to Streptococcal M1 Protein.},
  url          = {http://dx.doi.org/10.1128/IAI.00887-15},
  volume       = {83},
  year         = {2015},
}