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

Author

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

Subjects
NUCLEIC acids, STAPHYLOCOCCUS aureus, INFLAMMATION, KERATINOCYTES, STAPHYLOCOCCUS epidermidis, TOXIC shock syndrome
Abstract

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 cocultured 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. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Cross-specificity of protective human antibodies against Klebsiella pneumoniae LPS O-antigen

Author

Rollenske, Tim, Szijarto, Valeria, Lukasiewicz, Jolanta, Guachalla, Luis M., Stojkovic, Katarina, Hartl, Katharina, Stulik, Lukas, Kocher, Simone, Lasitschka, Felix, Al-Saeedi, Mohammed, Schröder-Braunstein, Jutta, von Frankenberg, Moritz, Gaebelein, Gereon, Hoffmann, Peter, Klein, Sabrina, Heeg, Klaus, Nagy, Eszter, Nagy, Gabor, and Wardemann, Hedda

Published
2018
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18. Incidences of Infectious Events in a Renal Transplant Cohort of the German Center of Infectious Diseases (DZIF)

Author

Sommerer, Claudia, Schroter, Iris, Gruneberg, Katrin, Schindler, Daniela, Behnisch, Rouven, Morath, Christian, Renders, Lutz, Heemann, Uwe, Schnitzler, Paul, Melk, Anette, Della Penna, Andrea, Nadalin, Silvio, Heeg, Klaus, Meuer, Stefan, Zeier, Martin, Giese, Thomas, Sommerer, Claudia, Schroter, Iris, Gruneberg, Katrin, Schindler, Daniela, Behnisch, Rouven, Morath, Christian, Renders, Lutz, Heemann, Uwe, Schnitzler, Paul, Melk, Anette, Della Penna, Andrea, Nadalin, Silvio, Heeg, Klaus, Meuer, Stefan, Zeier, Martin, and Giese, Thomas

Abstract

Background Infectious complications are a major cause of morbidity and mortality after kidney transplantation. Methods In this transplant cohort study at the German Center of Infectious Diseases (DZIF), we evaluated all infections occurring during the first year after renal transplantation. We assessed microbial etiology, incidence rates, and temporal occurrence of these infections. Results Of 804 renal transplant recipients (65.2% male, 51 +/- 14 years), 439 (54.6%) had 972 infections within the first year after transplantation. Almost half of these infections (47.8%) occurred within the first 3 months. Bacteria were responsible for 66.4% (645/972) of all infections, followed by viral (28.9% [281/972]) and fungal (4.7% [46/972]) pathogens. The urinary tract was the most common site of infection (42.4%). Enterococcus was the most frequently isolated bacterium (20.9%), followed by E. coli (17.6%) and Klebsiella (12.5%). E. coli was the leading pathogen in recipients <50 years of age, whereas Enterococcus predominated in older recipients. Resistant bacteria were responsible for at least 1 infection in 9.5% (76/804) of all recipients. Viral infections occurred in 201 recipients (25.0%). Of these, herpes viruses predominated (140/281 [49.8%]), and cytomegalovirus had the highest incidence rate (12.3%). In the 46 fungal infections, Candida albicans (40.8%) was the most commonly isolated. Other fungal opportunistic pathogens, including Aspergillus fumigatus and Pneumocystis, were rare. Conclusions Renal allograft recipients in Germany experience a high burden of infectious complications in the first year after transplantation. Bacteria were the predominating pathogen, followed by opportunistic infections such as cytomegalovirus. Microbial etiology varied between age groups, and resistant bacteria were identified in 10% of recipients.

Published
2022

26. Genomic Investigation and Successful Containment of an Intermittent Common Source Outbreak of OXA-48-Producing Enterobacter cloacae Related to Hospital Shower Drains

Author

Nurjadi, Dennis, primary, Scherrer, Martin, additional, Frank, Uwe, additional, Mutters, Nico T., additional, Heininger, Alexandra, additional, Späth, Isabel, additional, Eichel, Vanessa M., additional, Jabs, Jonas, additional, Probst, Katja, additional, Müller-Tidow, Carsten, additional, Brandt, Juliane, additional, Heeg, Klaus, additional, and Boutin, Sébastien, additional

Published
2021
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34. Association Between Soluble Notch Ligand Delta-like Ligand 1 and Bleeding Complications in Patients With Dengue Fever Infection

Author

Hildebrand, Dagmar, primary, Nurjadi, Dennis, additional, Hoan, Nghiem Xuan, additional, Linh, Mai Thanh Hai, additional, Sang, Vu Viet, additional, Bang, Mai Hong, additional, Pallerla, Srinivas Reddy, additional, Kremsner, Peter G, additional, Heeg, Klaus, additional, Song, Le Huu, additional, and Velavan, Thirumalaisamy P, additional

Published
2021
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41. Rapid Development of Cefiderocol Resistance in Carbapenem-resistant Enterobacter cloacae During Therapy Is Associated With Heterogeneous Mutations in the Catecholate Siderophore Receptor cirA

Author

Klein, Sabrina, primary, Boutin, Sébastien, additional, Kocer, Kaan, additional, Fiedler, Mascha O, additional, Störzinger, Dominic, additional, Weigand, Markus A, additional, Tan, Benjamin, additional, Richter, Daniel, additional, Rupp, Christian, additional, Mieth, Markus, additional, Mehrabi, Arianeb, additional, Hackert, Thilo, additional, Zimmermann, Stefan, additional, Heeg, Klaus, additional, and Nurjadi, Dennis, additional

Published
2021
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46. Extracellular ATP induces oscillations of intracellular [Ca.sup.2+] and membrane potential and promotes transcription of IL-6 in macrophages

Author

Hanley, Peter J., Musset, Boris, Renigunta, Vijay, Limberg, Sven H., Dalpke, Alexander H., Sus, Rainer, Heeg, Klaus M., Preisig-Muller, Regina, and Daut, Jurgen

Subjects
Macrophages -- Research, Science and technology
Abstract

The effects of low concentrations of extracellular ATP on cytosolic [Ca.sup.2+], membrane potential, and transcription of IL-6 were studied in monocyte-derived human macrophages. During inflammation or infection many cells secrete ATP. We show here that application of 10 [micro]M ATP or 10 [micro]M UTP induces oscillations in cytosolic [Ca.sup.2+] with a frequency of [approximately equal to] 12 [min.sup.-1] and oscillations in membrane potential. RT-PCR analysis showed expression of P2[Y.sub.1], P2[Y.sub.2], P2[Y.sub.11], P2[X.sub.1], P2[X.sub.4], and P2[X.sub.7] receptors, large-conductance (KCNMA1 and KCNMB1-4), and intermediate-conductance (KCNN4) [Ca.sup.2+]- activated [K.sup.+] channels. The [Ca.sup.2+] oscillations were unchanged after removal of extracellular [Ca.sup.2+], indicating that they were mainly due to movements of [Ca.sup.2+] between intracellular compartments. Comparison of the effects of different nucleotides suggests that the [Ca.sup.2+] oscillations were elicited by activation of P2[Y.sub.2] receptors coupled to phospholipase C. Patch-clamp experiments showed that ATP induced a transient depolarization, probably mediated by activation of P2[X.sub.4] receptors, followed by membrane potential oscillations due to opening of [Ca.sup.2+]- activated [K.sup.+] channels. We also found that 10 [micro]M ATP[gamma]S increased transcription of IL-6 [aproximately equal to] 40-fold within 2 h. This effect was abolished by blockade of P2Y receptors with 100 [micro]M suramin. Our results suggest that ATP released from inflamed, damaged, or metabolically impaired cells represents a 'danger signal' that plays a major role in activating the innate immune system.

Published
2004

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