Vigilant Keratinocytes Trigger PAMP Signaling in Response to Streptococcal M1 Protein.
(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:
https://lup.lub.lu.se/record/8034573
- author
- Persson, Sandra LU ; Wilk, Laura LU ; Mörgelin, Matthias LU and Herwald, Heiko LU
- organization
- publishing date
- 2015
- 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
- pmid:26416902
- ISSN
- 1098-5522
- DOI
- 10.1128/IAI.00887-15
- project
- Streptococcal skin infection project
- 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
- 2016-04-01 10:02:47
- date last changed
- 2022-04-27 18:02:52
@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 = {{https://lup.lub.lu.se/search/files/19313741/ASM_Persson_et_al.pdf}}, doi = {{10.1128/IAI.00887-15}}, volume = {{83}}, year = {{2015}}, }