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
Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's, Columbus, Ohio, USA.
Division of Nephrology and Hypertension, Nationwide Children's Hospital, Columbus, Ohio, USA.
J Innate Immun. 2023;15(1):865-875. doi: 10.1159/000534736. Epub 2023 Nov 18.
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.
越来越多的证据表明，属于核糖核酸酶A超家族的抗菌肽和蛋白质（AMPs）在保护膀胱和肾脏免受细菌感染方面起着关键作用。核糖核酸酶6已被鉴定为一种强效的、白细胞来源的AMPs，但其对体内尿路感染（UTI）的影响尚未得到证实。为了测试人核糖核酸酶6的功能作用，我们培育了RNASE6转基因小鼠，并研究了它们对实验性UTI的易感性。此外，我们培育了骨髓来源的巨噬细胞，以研究核糖核酸酶6在细胞环境中对抗菌活性的影响。与非转基因对照相比，当受到实验性UTI时，RNASE6转基因小鼠的尿路致病性大肠杆菌（UPEC）负荷、粘膜损伤和炎症有所减轻。在UTI期间，单核细胞和巨噬细胞是核糖核酸酶6的主要细胞来源，并且RNASE6转基因巨噬细胞在细胞内杀灭UPEC方面比非转基因对照更有效。总之，我们的研究结果表明人核糖核酸酶6在实验性UTI期间具有保护作用。
