Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection
Cortado, Hanna (The Abigail Wexner Research Institute at Nationwide Children's)
Kercsmar, Macie (Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's)
Li, Birong (The Abigail Wexner Research Institute at Nationwide Children's)
Vasquez-Martinez, Gabriela (The Abigail Wexner Research Institute at Nationwide Children's)
Gupta, Sudipti (The Abigail Wexner Research Institute at Nationwide Children's)
Ching, Christina (Nationwide Children's Hospital)
Ballash, Gregory (The Ohio State University)
Cotzomi-Ortega, Israel (The Abigail Wexner Research Institute at Nationwide Children's)
Sanchez-Zamora, Yuriko I. (The Abigail Wexner Research Institute at Nationwide Children's)
Boix i Borràs, Esther (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Zepeda-Orozco, Diana (Nationwide Children's Hospital)
Jackson, Ashley R. (Nationwide Children's Hospital)
Spencer, John David (Nationwide Children's Hospital)
Ruiz-Rosado, Juan de Dios (Nationwide Children's Hospital)
Becknell, Brian (Nationwide Children's Hospital)

Data:	2024
Resum:	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. We generated a Rnase6 EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6 EGFP/+ mice. Rnase6 deficiency (i. e. , Rnase6 EGFP/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. 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.
Ajuts:	Agencia Estatal de Investigación PID2019-106123GB-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Antimicrobial peptide ; Antimicrobial protein ; Bacterial infection ; Monocyte ; Macrophage ; Host defense ; Urinary tract infection ; Cystitis ; Pyelonephritis
Publicat a:	Journal of Innate Immunity, Vol. 16, Issue 1 (2024) , p. 283-294, ISSN 1662-8128

DOI: 10.1159/000539177
PMID: 38744252

12 p, 1.3 MB

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