Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.
J Innate Immun
; 16(1): 283-294, 2024.
Article
em En
| MEDLINE
| ID: mdl-38744252
ABSTRACT
INTRODUCTION:
The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI.METHODS:
We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility.RESULTS:
We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages.CONCLUSION:
Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ribonucleases
/
Infecções Urinárias
/
Camundongos Knockout
/
Infecções por Escherichia coli
/
Escherichia coli Uropatogênica
/
Macrófagos
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Innate Immun
Ano de publicação:
2024
Tipo de documento:
Article