Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection

Abstract Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract...

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Published inJournal of innate immunity Vol. 15; no. 1; pp. 865 - 875
Main Authors Ruiz-Rosado, Juan de Dios, Cortado, Hanna, Kercsmar, Macie, Li, Birong, Ballash, Gregory, Cotzomi-Ortega, Israel, Sanchez-Zamora, Yuriko I., Gupta, Sudipti, Ching, Christina, Boix, Ester, Jackson, Ashley R., Spencer, John David, Becknell, Brian
Format Journal Article
LanguageEnglish
Published Basel, Switzerland Karger Publishers 01.01.2023
Subjects
Animals
antimicrobial peptides
bacterial infection
cystitis
Endoribonucleases - genetics
host defense
Humans
Kidney
macrophage
Mice
Mice, Transgenic
Research Article
Ribonucleases - genetics
Urinary Bladder - microbiology
urinary tract infection
Urinary Tract Infections
Bacterial infection
Urinary tract infection
Host defense
Cystitis
Antimicrobial peptides
Macrophage
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Summary:Abstract Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.
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ISSN:1662-811X
1662-8128
DOI:10.1159/000534736