IL-17C is an important epithelial cell-derived cytokine activating innate immunity by the induction of antimicrobial peptides and cytokines. Here, we investigated the role of the cytosolic pattern recognition receptor nucleotide-binding oligomerization domain-containing protein 2 (NOD2) for the Staphylococcus aureus-mediated induction of IL-17C. Activation of NOD2 in HEK293 cells overexpressing NOD2 induced the IL-17C promoter, an activity that was significantly reduced in cells overexpressing the Crohn's disease-associated NOD2 mutation 3020insC (1007fs) or the Crohn's disease- and atopic dermatitis-associated NOD2-R702W variant. The first NF-κB-binding site in the IL-17C promoter was critical for NOD2-mediated IL-17C induction. Infection of human primary keratinocytes with S. aureus induced NOD2 and IL-17C gene expression. Overexpression of NOD2 in keratinocytes augmented S. aureus-mediated IL-17C gene expression as compared with NOD2-R702W overexpression. S. aureus-induced IL-17C expression was diminished in NOD2 small interfering RNA (siRNA)-treated keratinocytes. Moreover, significantly less S. aureus bacteria survived in keratinocytes overexpressing NOD2 but not in cells overexpressing the NOD2-R702W variant. Finally, S. aureus showed an increased survival in keratinocytes treated with NOD2 or IL-17C siRNA. In summary, our study provides evidence that S. aureus activates NOD2 in keratinocytes, resulting in an increased expression of IL-17C, a mechanism that may be dysregulated in atopic dermatitis.

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Neuroblastoma is the most common diagnosed tumor in infants and the second most common extracranial tumor of childhood. The survival rate of patients with high-risk neuroblastoma is still very low despite intensive multimodal treatments. Therefore, new treatment strategies are needed. In recent years, miRNA-based anticancer therapy has received growing attention. Advances in this novel treatment strategy strongly depends on the identification of candidate miRNAs with broad-spectrum antitumor activity. Here, we identify miR-193b as a miRNA with tumor suppressive properties. We show that miR-193b is expressed at low levels in neuroblastoma cell lines and primary tumor samples. Introduction of miR-193b mimics into nine neuroblastoma cell lines with distinct genetic characteristics significantly reduces cell growth in vitro independent of risk factors such as p53 functionality or MYCN amplification. Functionally, miR-193b induces a G1 cell cycle arrest and cell death in neuroblastoma cell lines by reducing the expression of MYCN, Cyclin D1 and MCL-1, three important oncogenes in neuroblastoma of which inhibition has shown promising results in preclinical testing. Therefore, we suggest that miR-193b may represent a new candidate for miRNA-based anticancer therapy in neuroblastoma.

IntroductionThe emergence of carbapenem-resistant bacteria causing serious infections may lead to more frequent use of previously abandoned antibiotics like colistin. However, mobile colistin resistance genes (mcr) can jeopardise its effectiveness in both human and veterinary medicine. In Germany, turkeys have been identified as the food-producing animal most likely to harbour mcr-positive colistin-resistant Enterobacterales (mcr-Col-E). Therefore, the aim of the present study was to assess the prevalence of both mcr-Col-E and carbapenemase-producing Enterobacterales (CPE) in German turkey herds and humans in contact with these herds.MethodsIn 2018 and 2019, 175 environmental (boot swabs of turkey faeces) and 46 human stool samples were analysed using a combination of enrichment-based culture, PCR, core genome multilocus sequence typing (cgMLST) and plasmid typing.Resultsmcr-Col-E were detected in 123 of the 175 turkey farms in this study (70.3%). mcr-Col-E isolates were Escherichia coli (98.4%) and Klebsiella spp. (1.6%). Herds that had been treated with colistin were more likely to harbour mcr-Col-E, with 82.2% compared to 66.2% in untreated herds (p = 0.0298). Prevalence also depended on husbandry, with 7.1% mcr-Col-E in organic farms compared to 74.5% in conventional ones (p < 0.001). In addition, four of the 46 (8.7%) human participants were colonised with mcr-Col-E. mcr-Col-E isolates from stables had minimum inhibitory concentrations (MICs) from 4 to ≥ 32 mg/L, human isolates ranged from 4 to 8 mg/L. cgMLST showed no clonal transmission of isolates. For one farm, plasmid typing revealed great similarities between plasmids from an environmental and a human sample. No CPE were found in turkey herds or humans.DiscussionThese findings confirm that mcr-Col-E-prevalence is high in turkey farms, but no evidence of direct zoonotic transmission of clonal mcr-Col-E strains was found. However, the results indicate that plasmids may be transmitted between E. coli isolates from animals and humans.

similar risk was observed for breastfeeding 9-11 compared to breastfeeding !12 months. Conclusions Full breastfeeding for 6 months was associated with a reduction in hospitalisation for infections compared with absent or partial breastfeeding from <4 months, but not compared to full breastfeeding for 4 months. Reduced risk of hospitalisation was found with any breastfeeding up to 9 months' age but not beyond.