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Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli

Nature Medicine volume 7, pages 801–806 (2001)Cite this article

Abstract

To assess the role of complement in renal infection, we studied a model of Escherichia coli-induced pyelonephritis in mice deficient in complement components C3 and C4. Renal infection occurred less frequently in C3- and C4-deficient mice compared with wild-type mice. In vitro, renal epithelial cells internalized fewer bacteria in the absence of C3 or in the presence of blockade of C3 bound to the bacteria. Moreover, upregulation of epithelial C3 production by stimulation with lipopolysaccharide enhanced bacterial internalization. Here we provide evidence that uropathogenic E. coli might use host C3 to invade the renal epithelium and that local complement production is sufficient for the bacteria to achieve this effect.

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Figure 1: Internalization of E. coli into proximal tubular epithelial cells.
Figure 2: The effect of pre-incubation with serum.
Figure 3: C3 expression by proximal tubular epithelial cells.
Figure 4: Effect of local complement synthesis on bacterial internalization.
Figure 5: Crry expression on urinary tract epithelial cells and in vitro blockade of C3-receptor interaction with Crry–Ig.

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Authors and Affiliations

  1. Department of Nephrology and Transplantation, Guy's Hospital, GKT, King's College London, UK

    Tabitha Springall, Neil S. Sheerin, Katsushige Abe & Steven H. Sacks

  2. Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, Colorado, USA

    V. Michael Holers

  3. Department of Cell and Molecular Pathology, St John's Institute of Dermatology, St Thomas' Hospital, GKT, King's College London, UK

    Hong Wan

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  1. Tabitha Springall
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  2. Neil S. Sheerin
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Correspondence to Neil S. Sheerin.

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Springall, T., Sheerin, N., Abe, K. et al. Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli. Nat Med 7, 801–806 (2001). https://doi.org/10.1038/89923

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