1. The Antimicrobial and Immunomodulatory Function of RNase 7 in Skin
Franziska Rademacher, Sylvia Dreyer, Verena Kopfnagel, Regine Gläser, Thomas Werfel, Jürgen Harder Front Immunol. 2019 Nov 5;10:2553. doi: 10.3389/fimmu.2019.02553. eCollection 2019.
The human ribonuclease RNase 7 has been originally isolated from human skin and is a member of the human RNase A superfamily. RNase 7 is constantly released by keratinocytes and accumulates on the skin surface. The expression of RNase 7 in keratinocytes can be induced by diverse stimuli such as cytokines, growth factors, and microbial factors. RNase 7 exhibits a potent broad spectrum of antimicrobial activity against various microorganisms and contributes to control bacterial growth on the skin surface. The ribonuclease and antimicrobial activity of RNase 7 can be blocked by the endogenous ribonuclease inhibitor. There is also increasing evidence that RNase 7 exerts immunomodulatory activities and may participate in antiviral defense. In this review, we discuss how these characteristics of RNase 7 contribute to innate cutaneous defense and highlight its role in skin infection and inflammation. We also speculate how a potential dysregulation of RNase 7 promotes inflammatory skin diseases and if RNase 7 may have therapeutic potential.
2. Ribonuclease 7 polymorphism rs1263872 reduces antimicrobial activity and associates with pediatric urinary tract infections
Keith R Pierce, Tad Eichler, Claudia Mosquera Vasquez, Andrew L Schwaderer, Aaron Simoni, Steven Creacy, David S Hains, John D Spencer J Clin Invest. 2021 Nov 15;131(22):e149807. doi: 10.1172/JCI149807.
Ribonuclease 7 (RNase 7) is an antimicrobial peptide that prevents urinary tract infections (UTI); however, it is yet unknown how RNASE7 genetic variations affect its antimicrobial activity and its mitigation of UTI risk. This study determined whether the RNASE7 SNP rs1263872 is more prevalent in children with UTI and defined how rs1263872 affects RNase 7's antimicrobial activity against uropathogenic E. coli (UPEC). We performed genotyping for rs1263872 in 2 national UTI cohorts, including children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux trial or the Careful Urinary Tract Infection Evaluation study. Genotypes from these cohorts were compared with those of female controls with no UTI. To assess whether rs1263872 affects RNase 7's antimicrobial activity, we generated RNase 7 peptides and genetically modified urothelial cultures encoding wild-type RNase 7 and its variant. Compared with controls, girls in both UTI cohorts had an increased prevalence of the RNASE7 variant. Compared with the missense variant, wild-type RNase 7 peptide showed greater bactericidal activity against UPEC. Wild-type RNase 7 overexpression in human urothelial cultures reduced UPEC invasive infection compared with mutant overexpression. These results show that children with UTI have an increased prevalence of RNASE7 rs1263872, which may increase UTI susceptibility by suppressing RNase 7's antibacterial activity.
3. Antimicrobial Synergy of a Ribonuclease and a Peptide Secreted by Human Cells
Chelcie H Eller, Ronald T Raines ACS Infect Dis. 2020 Nov 13;6(11):3083-3088. doi: 10.1021/acsinfecdis.0c00594. Epub 2020 Oct 15.
LL-37 is a secretory peptide that has antimicrobial activity. Ribonuclease 1 (RNase 1) is a secretory enzyme that is not cytotoxic. We find that human LL-37 and human RNase 1 can act synergistically to kill Gram-negative bacterial cells. In the presence of nontoxic concentrations of LL-37, RNase 1 is toxic to Escherichia coli cells at picomolar levels. Using wild-type RNase 1 and an inactive variant labeled with a fluorophore, we observe the adherence of RNase 1 to E. coli cells and its cellular entry in the presence of LL-37. These data suggest a natural means of modulating the human microbiome via the cooperation of an endogenous peptide (37 residues) and small enzyme (128 residues).
