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Methods ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02744

High Resolution Intravital Imaging of the Renal Immune Response to Injury and Infection in Mice.

  • 1Department of Medical Cell Biology, Uppsala University, Sweden
  • 2Swedish Medical Nanoscience Center, Karolinska Institutet, Sweden

Urinary tract infections caused by uropathogenic Escherichia coli are one of the most common infections, and can lead to sepsis or end-stage renal failure. To be able study the pathology of kidney infection longitudinally, we developed an experimental set up that enables long-term studies of immune cell behavior in situ in the challenged as well as unchallenged kidney of anesthetized mice. Using highly controlled vacuum to stabilize the kidney, the superficial renal cortex was continuously visualized with minimal disruption of the local microenvironment. No visible changes in blood flow or neutrophils, monocytes and macrophages numbers were observed over several hours of visualizing the unchallenged kidney, indicating a stable tissue preparation without apparent tissue damage. Applying this set up to monocyte/macrophage (CX3CR1GFP/+) reporter mice, we observed an extensive network of stellate-shaped CX3CR1 positive cells (previously identified as renal mononuclear phagocytes) as well as intravascular neutrophils that crawl within the microvasculature of the healthy kidney. The extended dendrites of the CX3CR1 positive cells were found to bridge multiple capillaries and tubules and were in constant motion. Light induced sterile tissue injury resulted in rapid neutrophil recruitment to the site of injury. Microinfusion of uropathogenic Escherichia coli into a single nephron induced a rapid and massive recruitment of neutrophils to the site of infection, in addition to active bacterial clearance by neutrophils. In contrast, the kidney resident mononuclear phagocytes did not increase in numbers or migrate towards the site of injury or infection. In conclusion, this model allows for longitudinal imaging of host responses to localized kidney challenges and highlights the extensive network of renal phagocytes and their behavior in vivo in health and disease.

Keywords: intravital, Renal infection, Neutrophils, Macrophages, Mononuclear phagocyte, Sterile injury

Received: 14 Jun 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Sedin, Giraud, Steiner, Ahl, Persson, Melican, Richter-Dahlfors and Phillipson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Mia Phillipson, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden, mia.phillipson@mcb.uu.se