Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein
| Autor: | Matthias Mörgelin, Heiko Herwald, Sandra Persson, Laura Wilk |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Keratinocytes
MAPK/ERK pathway Streptococcus pyogenes Mitogen-Activated Protein Kinase 3 Chemokine CXCL1 p38 mitogen-activated protein kinases Immunology Interleukin-1 Receptor-Like 1 Protein Receptors Cell Surface Biology medicine.disease_cause p38 Mitogen-Activated Protein Kinases Microbiology Proinflammatory cytokine Interleukin-1alpha medicine Humans Protein kinase A Macrophage Migration-Inhibitory Factors Cell Line Transformed Mitogen-Activated Protein Kinase 1 Antigens Bacterial Host Response and Inflammation Interleukin-8 Intracellular Signaling Peptides and Proteins NF-kappa B Toll-Like Receptor 2 Cell biology Intramolecular Oxidoreductases Transcription Factor AP-1 Interleukin 1 Receptor Antagonist Protein Infectious Diseases Gene Expression Regulation Host-Pathogen Interactions Basigin Parasitology Signal transduction Carrier Proteins Bacterial Outer Membrane Proteins Signal Transduction |
| Zdroj: | Infection and Immunity. 83:4673-4681 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | 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 pathogen-associated molecular pattern to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal protein kinase and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of the inflammatory mediators released, such as interleukin-8 (IL-8), growth-related oncogene alpha, migration inhibitory factor, extracellular matrix metalloproteinase inducer, IL-1α, IL-1 receptor a, and ST2, in response to streptococcal M1 protein. The expression of IL-8 is dependent on Toll-like receptor 2 activity and subsequent activation of the mitogen-activated protein kinases ERK and p38. Notably, this signaling seems to be distinct for IL-8 release, and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate in a proinflammatory manner in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein. |
| Databáze: | OpenAIRE |
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