Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes

Staphylococcus aureus is one of the clinically most relevant pathogens causing infections. Humans are often exposed to S. aureus. In approximately one-third of the healthy population it can be found on the skin either for long or short periods as colonizing “commensals”, without inducing infections...

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Main Authors: Quang Vinh Ngo, Larissa Faass, Aline Sähr, Dagmar Hildebrand, Tatjana Eigenbrod, Klaus Heeg, Dennis Nurjadi
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.828626/full
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author Quang Vinh Ngo
Quang Vinh Ngo
Larissa Faass
Larissa Faass
Aline Sähr
Dagmar Hildebrand
Tatjana Eigenbrod
Klaus Heeg
Klaus Heeg
Dennis Nurjadi
Dennis Nurjadi
author_facet Quang Vinh Ngo
Quang Vinh Ngo
Larissa Faass
Larissa Faass
Aline Sähr
Dagmar Hildebrand
Tatjana Eigenbrod
Klaus Heeg
Klaus Heeg
Dennis Nurjadi
Dennis Nurjadi
author_sort Quang Vinh Ngo
collection DOAJ
description Staphylococcus aureus is one of the clinically most relevant pathogens causing infections. Humans are often exposed to S. aureus. In approximately one-third of the healthy population it can be found on the skin either for long or short periods as colonizing “commensals”, without inducing infections or an inflammatory immune response. While tolerating S. aureus seems to be limited to certain individuals and time periods in most cases, Staphylococcus epidermidis is tolerated permanently on the skin of almost all individuals without activating overwhelming skin inflammation. To investigate this, we co-cultured a keratinocyte cell line (HaCaT) with viable S. aureus or S. epidermidis to study the differences in the immune activation. S. aureus activated keratinocytes depicted by a profound IL-6 and IL-8 response, whereas S. epidermidis did not. Our data indicate that internalization of S. aureus and the subsequent intracellular sensing of bacterial nucleic acid may be essential for initiating inflammatory response in keratinocytes. Internalized dsRNA activates IL-6 and IL-8 release, but not TNF-α or IFNs by human keratinocytes. This is a non-specific effect of dsRNA, which can be induced using Poly(I:C), as well as RNA from S. aureus and S. epidermidis. However, only viable S. aureus were able to induce this response as these bacteria and not S. epidermidis were actively internalized by HaCaT. The stimulatory effect of S. aureus seems to be independent of the TLR3, -7 and -8 pathways.
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spelling doaj.art-26f9d96ccd59412ab0078931db9e32762024-03-06T08:51:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.828626828626Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in KeratinocytesQuang Vinh Ngo0Quang Vinh Ngo1Larissa Faass2Larissa Faass3Aline Sähr4Dagmar Hildebrand5Tatjana Eigenbrod6Klaus Heeg7Klaus Heeg8Dennis Nurjadi9Dennis Nurjadi10Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyMax von Pettenkofer Institute, Chair for Medical Microbiology and Hygiene, Ludwig Maximilians University Munich, Munich, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, GermanyDepartment of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, GermanyDeutsches Zentrum für Infektionsforschung (DZIF), Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, GermanyStaphylococcus aureus is one of the clinically most relevant pathogens causing infections. Humans are often exposed to S. aureus. In approximately one-third of the healthy population it can be found on the skin either for long or short periods as colonizing “commensals”, without inducing infections or an inflammatory immune response. While tolerating S. aureus seems to be limited to certain individuals and time periods in most cases, Staphylococcus epidermidis is tolerated permanently on the skin of almost all individuals without activating overwhelming skin inflammation. To investigate this, we co-cultured a keratinocyte cell line (HaCaT) with viable S. aureus or S. epidermidis to study the differences in the immune activation. S. aureus activated keratinocytes depicted by a profound IL-6 and IL-8 response, whereas S. epidermidis did not. Our data indicate that internalization of S. aureus and the subsequent intracellular sensing of bacterial nucleic acid may be essential for initiating inflammatory response in keratinocytes. Internalized dsRNA activates IL-6 and IL-8 release, but not TNF-α or IFNs by human keratinocytes. This is a non-specific effect of dsRNA, which can be induced using Poly(I:C), as well as RNA from S. aureus and S. epidermidis. However, only viable S. aureus were able to induce this response as these bacteria and not S. epidermidis were actively internalized by HaCaT. The stimulatory effect of S. aureus seems to be independent of the TLR3, -7 and -8 pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2022.828626/fullStaphylococcus aureusStaphylococcus epidermidiskeratinocyteskin immune responsebacterial RNAhost-pathogen interaction
spellingShingle Quang Vinh Ngo
Quang Vinh Ngo
Larissa Faass
Larissa Faass
Aline Sähr
Dagmar Hildebrand
Tatjana Eigenbrod
Klaus Heeg
Klaus Heeg
Dennis Nurjadi
Dennis Nurjadi
Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes
Frontiers in Immunology
Staphylococcus aureus
Staphylococcus epidermidis
keratinocyte
skin immune response
bacterial RNA
host-pathogen interaction
title Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes
title_full Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes
title_fullStr Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes
title_full_unstemmed Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes
title_short Inflammatory Response Against Staphylococcus aureus via Intracellular Sensing of Nucleic Acids in Keratinocytes
title_sort inflammatory response against staphylococcus aureus via intracellular sensing of nucleic acids in keratinocytes
topic Staphylococcus aureus
Staphylococcus epidermidis
keratinocyte
skin immune response
bacterial RNA
host-pathogen interaction
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.828626/full
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