Kidney Week

Abstract: SA-OR46

Cross-Talk Between Neutrophils and Macrophages Dictates the Outcome of Acute Pyelonephritis

Session Information

• Pediatric Nephrology and Development: Research Abstracts
  October 24, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Pediatric Nephrology

• 1700 Pediatric Nephrology

Authors

• Ruiz-Rosado, Juan de Dios, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States

Juan de Dios Ruiz-Rosado, PhD



My name is Juan de Dios Ruiz Rosado, I am a postdoctoral research scientist at the Abigail Wexner Research Institute, Nationwide Children’s Hospital (NCH). I am a proud member of the Nephrology and Urology Research Affinity Group (NURAG) at NCH. My research focuses on elucidating the functional roles of immune phagocytes in the development of kidney fibrosis and the consequent impairment of renal function during urinary tract infections (UTI). I am enthusiastic and committed to become an accomplished independent investigator, and develop a comprehensive understanding of the protective cellular mechanisms elicited during UTI. My overarching goal is to advance the delivery of more targeted interventions to control the development of adverse sequelae in children with UTI.

• Cortado, Hanna H., Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States

Hanna H. Cortado,

• Spencer, John David, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States

John David Spencer,

• Becknell, Brian, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States

Brian Becknell,

• Partida-Sanchez, Santiago, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, United States

Santiago Partida-Sanchez,

Background

Pediatric urinary tract infections (UTI) account for 1.5 million clinician visits annually in the United States. Uropathogenic Escherichia coli (UPEC) causes over 80% of UTIs. Up to 50% of infants with a UTI develop a kidney infection (acute pyelonephritis, APN). Despite prompt diagnosis and treatment with appropriate antibiotics, a population of children with APN develops renal scarring, which can lead to kidney injury and renal dysfunction. The cellular immune mechanisms underlying renal scarring after an APN episode remain incompletely understood. In this study, we determined the contribution of neutrophils and monocytes to the development of kidney pathology following experimental APN.

Methods

C3H/HeOuJ female mice were treated with monoclonal antibodies to deplete neutrophils (anti-Ly6G), monocytes (anti-CD115), or both neutrophils and monocytes (anti-Gr1). After cell depletion, the animals were transurethrally infected with UPEC strain CFT073. Bacterial ascent was assessed via biophotonic imaging and quantification of bacterial burden in the kidney. The cell dynamics of monocytes and neutrophils were determined by flow cytometry and immunofluorescence microscopy. Renal inflammation and fibrosis were assessed by H&E and Sirius-Red, respectively. Transcriptomic analyses of infected kidneys were performed using TaqMan Arrays.

Results

Our data indicate that neutrophils, not monocytes, are required to prevent widespread UPEC dissemination during APN. In contrast, monocyte-derived macrophages promote bacterial dissemination and induce an early inflammatory response upon UPEC infection. Exacerbated, macrophage-dependent inflammation during APN leads to increased renal abscess formation, tubular injury, renal fibrosis, and azotemia.

Conclusion

While highlighting the essential antimicrobial role for neutrophils, our findings point to a novel detrimental function for macrophages during APN, and the potential utility of macrophage targeted therapies to reduce long-term sequelae following APN.

Funding

• NIDDK Support