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High Resolution Intravital Imaging of the Renal Immune Response to Injury and Infection in Mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.ORCID iD: 0000-0002-8559-5781
Karolinska Inst, Dept Neurosci, Swedish Med Nanosci Ctr, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2744Article in journal (Refereed) Published
Abstract [en]

We developed an experimental set up that enables longitudinal studies of immune cell behavior in situ in the challenged as well as unchallenged kidney of anesthetized mice over several hours. Using highly controlled vacuum to stabilize the kidney, the superficial renal cortex could continuously be visualized with minimal disruption of the local microenvironment. No visible changes in blood flow or neutrophils and macrophages numbers were observed after several hours of visualizing the unchallenged kidney, indicating a stable tissue preparation without apparent tissue damage. Applying this set up to monocyte/macrophage (CX(3)CR1(GFP/+)) reporter mice, we observed the extensive network of stellate-shaped CX(3)CR1 positive cells (previously identified as renal mononuclear phagocytes). The extended dendrites of the CX(3)CR1 positive cells were found to bridge multiple capillaries and tubules and were constantly moving. Light induced sterile tissue injury resulted in rapid neutrophil accumulation to the site of injury. Similarly, 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 were observed to not increase in numbers or migrate toward the site of injury or infection. In conclusion, this model allows for longitudinal imaging of responses to localized kidney challenges in the mouse.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019. Vol. 10, article id 2744
Keywords [en]
intravital, renal infection, neutrophils, macrophages, mononuclear phagocytes, sterile injury
National Category
Immunology in the medical area Immunology
Identifiers
URN: urn:nbn:se:uu:diva-402374DOI: 10.3389/fimmu.2019.02744ISI: 000504216500001PubMedID: 31921099OAI: oai:DiVA.org:uu-402374DiVA, id: diva2:1389410
Funder
Swedish Foundation for Strategic Research Swedish Research Council, 2018-02552Knut and Alice Wallenberg FoundationRagnar Söderbergs stiftelseNovo NordiskAvailable from: 2020-01-29 Created: 2020-01-29 Last updated: 2020-01-29Bibliographically approved

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