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Innate immunity during UTI and skin infection

Why are some patients more susceptible to infections?

Urinary tract infections (UTIs) belong to the most common bacterial infections worldwide and are primarily caused by uropathogenic Escherichia coli. To infect and remain in the urinary tract, E. coli are equipped with a variety of virulence factors, which allow colonisation of the tissue and evade the innate immune defence mechanisms of the host. We investigate this struggle of host and pathogen from both sides. As our research focuses on clinical issues, most of our studies are based on clinical material. Using established cell culture systems, molecular techniques, and mouse models in combination with clinical samples, we can reveal why some patient groups are more susceptible to UTIs. 

Repurposing common drugs to increase the innate immune response

Infections, including UTIs, are common in patients with diabetes. However, treatment with antibiotics is becoming a major problem due to increasing resistance. In this line, we are continuing to focus on how diabetes affects the production of antimicrobial peptides and innate immunity. In addition to analysing the effect of diabetes on host defence, we investigate how repurposing of certain drugs, such as hypoxia-inducible factor 1 activators, and the antidiabetic drug metformin, can strengthen uroepithelial immunity by stimulating resident uroepithelial cells to produce the antimicrobial peptides LL-37 and RNase 7, in addition to triggering expression of pro-inflammatory cytokines. 

Novel gels an alternative to treat skin infections

Skin infections are common amongst all age groups, but are more prevalent and dangerous amongst patients with long term systemic disease. Recently, we showed that a novel cationic hydrogel based on amino-functional hyperbranched dendritic-linear-dendritic copolymers exhibit striking antimicrobial activity towards clinical skin pathogens (including drug-resistant strains). In addition to the direct antibacterial activity, we observed that the hydrogels could induce the expression of important antimicrobial peptides in human skin, including RNase 7 and psoriasin. This dual-sided activity of the compound are promising for designing compounds, such as nanomaterials or novel synthetic AMPs, for combating infection and strengthening innate defence mechanisms, which is one of the research lines that we follow now.