The role of myeloid immune cells in healing and recurrence of pyelonephritis
Year: 2026
Type: dissertation
Abstract: Urinary tract infections (UTIs), the second most common type of infection globally, pose a substantial burden on healthcare systems. They include infections of the bladder, known as cystitis, and infections of the kidneys, referred to as pyelonephritis (PN). UTIs are characterized by a high rate of recurrence, which can lead to chronic symptoms and, in some cases, severe complications. Due to the high level of bacterial resistance to antibiotics, a comprehensive understanding of the mechanisms leading to and driving PN is essential for the development of non-antibiotic therapeutic strategies and for improving existing antibiotic treatments. Within the scope of this thesis, we investigated the role of monocytes in acute and chronic PN. Fibrotic kidneys were rich in classical monocytes, whereas non-fibrotic kidneys showed an abundance of non-classical monocytes. Deficiency in monocytes in CCR2-/- mice attenuated acute infection and reduced renal scarring in chronic PN model. Classical monocytes isolated from infected kidneys stimulated fibroblasts to produce collagen in vitro. Proteomic analysis of fibrotic kidneys revealed distinct changes associated with renal fibrosis. We identified IL-36α as the most upregulated cytokine and confirmed its expression in the kidney. We also identified renal mononuclear phagocytes (MNPs) as reservoirs of UPEC, which use complement receptors 3 and 4 subunits, CD11b and CD11c respectively, for bacterial uptake. We demonstrated that UPEC is able to survive inside MNPs and that intracellular antibiotic treatment is more effective than therapy with an extracellular antibiotic. Blocking CD11b and CD11c reduced bacterial burden in the kidney and improved extracellularly working antibiotic therapy efficiency. In summary, we described monocytes and IL-36α as potential fibrosis mediators and MNPs as a niche for UPEC survival, contributing to relapse.
Source: bonndoc (University of Bonn)
DOI: 10.48565/bonndoc-961
Author: Goldyn, Beata Ewa
Institution: University of Bonn
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7212057690
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