Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection
Ruiz-Rosado, Juan de Dios (Nationwide Children's Hospital)
Cortado, Hanna (The Abigail Wexner Research Institute at Nationwide Children's)
Kercsmar, Macie (The Abigail Wexner Research Institute at Nationwide Children's)
Li, Birong (The Abigail Wexner Research Institute at Nationwide Children's)
Ballash, Gregory (The Abigail Wexner Research Institute at Nationwide Children's)
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)
Gupta, Sudipti (The Abigail Wexner Research Institute at Nationwide Children's)
Ching, Christina (Nationwide Children's Hospital)
Boix i Borràs, Esther (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Jackson, Ashley R. (Nationwide Children's Hospital)
Spencer, John David (Nationwide Children's Hospital)
Becknell, Brian (Nationwide Children's Hospital)

Fecha:	2023
Resumen:	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.
Ayudas:	Agencia Estatal de Investigación PID2019-106123GB-I00
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Antimicrobial peptides ; Bacterial infection ; Macrophage ; Host defense ; Urinary tract infection ; Cystitis
Publicado en:	Journal of Innate Immunity, Vol. 15, Issue 1 (November 2023) , p. 865-875, ISSN 1662-8128

DOI: 10.1159/000534736
PMID: 37980892

11 p, 1.1 MB

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