Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder

Soumitra Mohanty, Witchuda Kamolvit, Andrea Scheffschick, Anneli Björklund, Jonas Tovi, Alexander Espinosa, Kerstin Brismar, Thomas Nyström, Jens M. Schröder, Claes-Göran Östenson, Pontus Aspenström, Hanna Brauner and Annelie Brauner ()
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Soumitra Mohanty: Karolinska Institutet
Witchuda Kamolvit: Karolinska Institutet
Andrea Scheffschick: Department of Medicine
Anneli Björklund: Center for Diabetes, Academic Specialist Center, Stockholm County Council
Jonas Tovi: Capio Health Care Center
Alexander Espinosa: Department of Medicine
Kerstin Brismar: Karolinska Institutet
Thomas Nyström: Division of Internal Medicine, Unit for Diabetes Research, Karolinska Institutet, South Hospital
Jens M. Schröder: University Hospital Schleswig-Holstein
Claes-Göran Östenson: Karolinska Institutet
Pontus Aspenström: Uppsala University
Hanna Brauner: Department of Medicine
Annelie Brauner: Karolinska Institutet

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity.

Date: 2022
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DOI: 10.1038/s41467-022-32636-y

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