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Uropathogen and host responses in pyelonephritis

Nature Reviews Nephrology volume 19, pages 658–671 (2023)Cite this article

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Abstract

Urinary tract infections (UTIs) are among the most common bacterial infections seen in clinical practice. The ascent of UTI-causing pathogens to the kidneys results in pyelonephritis, which can trigger kidney injury, scarring and ultimately impair kidney function. Despite sizable efforts to understand how infections develop or are cleared in the bladder, our appreciation of the mechanisms by which infections develop, progress or are eradicated in the kidney is limited. The identification of virulence factors that are produced by uropathogenic Escherichia coli to promote pyelonephritis have begun to fill this knowledge gap, as have insights into the mechanisms by which kidney tubular epithelial cells oppose uropathogenic E. coli infection to prevent or eradicate UTIs. Emerging data also illustrate how specific cellular immune responses eradicate infection whereas other immune cell populations promote kidney injury. Insights into the mechanisms by which uropathogenic E. coli circumvent host immune defences or antibiotic therapy to cause pyelonephritis is paramount to the development of new prevention and treatment strategies to mitigate pyelonephritis and its associated complications.

Key points

  • Uropathogenic Escherichia coli (UPEC) is the most common bacterial cause of pyelonephritis; virulence factors expressed by UPEC promote survival in the kidney by expediating cellular invasion and neutralizing host defences.

  • Within the collecting duct, intercalated cells are targeted by UPEC; intercalated cells respond by activating acid–base machinery, phagocytosing bacteria, producing cytokines and chemokines and releasing antimicrobial peptides.

  • An intricate network of macrophages and dendritic cells, in close proximity to collecting tubules, survey the renal interstitium and respond to UPEC by producing neutrophil and monocyte chemoattractants to combat bacteria during pyelonephritis.

  • Extracellular environmental factors and endogenous hormones influence or control important antibacterial defences in the kidney.

  • The increasing prevalence of antibiotic-resistant uropathogens highlights an urgent need for new therapeutic approaches that conserve antibiotic use and mitigate the morbidity associated with pyelonephritis; better understanding of host–pathogen interactions in the kidney may aid these efforts.

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Fig. 1: Antibiotic targets and antibiotic resistance strategies deployed by uropathogenic Escherichia coli.
Fig. 2: Antibacterial responses of the kidney collecting duct to uropathogenic Escherichia coli.
Fig. 3: Emerging and potential antibiotic-conserving therapeutics for pyelonephritis.

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Acknowledgements

We apologize to the authors whose important work could not be included in this article owing to space limitations. J.D.S. discloses support for publication of this work from the National Institutes of Health (NIDDK) R01 DK115737, DK114035, and DK128088 (J.D.S.). J.D.R.R. discloses support by the National Institutes of Health (NIDDK) K01 DK128379.

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  1. The Kidney and Urinary Tract Center, Nationwide Children’s Abigail Wexner Research Institute, Columbus, OH, USA

    Laura Schwartz, Juan de Dios Ruiz-Rosado, Emily Stonebrook, Brian Becknell & John David Spencer

  2. The Ohio State University College of Medicine, Columbus, OH, USA

    Laura Schwartz, Juan de Dios Ruiz-Rosado, Emily Stonebrook, Brian Becknell & John David Spencer

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All authors contributed to the design of the manuscript and edited the final product. E.S. wrote the introduction and the section on the clinical implications of pyelonephritis; L.S. wrote the sections on antibiotic resistance and bacterial virulence factors, and created the figures; B.B. and J.D.R.R. wrote the sections on immune cells; and J.D.S. wrote the sections on epithelial responses during pyelonephritis.

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Schwartz, L., de Dios Ruiz-Rosado, J., Stonebrook, E. et al. Uropathogen and host responses in pyelonephritis. Nat Rev Nephrol 19, 658–671 (2023). https://doi.org/10.1038/s41581-023-00737-6

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