AUTHOR=Ngo Quang Vinh , Faass Larissa , Sähr Aline , Hildebrand Dagmar , Eigenbrod Tatjana , Heeg Klaus , Nurjadi Dennis 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.828626

DOI=10.3389/fimmu.2022.828626

ISSN=1664-3224

ABSTRACT=<p><italic>Staphylococcus aureus</italic> is one of the clinically most relevant pathogens causing infections. Humans are often exposed to <italic>S. aureus</italic>. 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 <italic>S. aureus</italic> seems to be limited to certain individuals and time periods in most cases, <italic>Staphylococcus epidermidis</italic> 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 <italic>S. aureus</italic> or <italic>S. epidermidis</italic> to study the differences in the immune activation<italic>. S. aureus</italic> activated keratinocytes depicted by a profound IL-6 and IL-8 response, whereas <italic>S. epidermidis</italic> did not. Our data indicate that internalization of <italic>S. aureus</italic> 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 <italic>S. aureus</italic> and <italic>S. epidermidis</italic>. However, only viable <italic>S. aureus</italic> were able to induce this response as these bacteria and not <italic>S. epidermidis</italic> were actively internalized by HaCaT. The stimulatory effect of <italic>S. aureus</italic> seems to be independent of the TLR3, -7 and -8 pathways.</p>