Role of myeloid immune cells in healing and recurrence of pyelonephritis

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Pyelonephritis (PN) is an infection of the kidneys occurring as a complication of urinary tract infection which ascends from the bladder to the kidneys. The main pathogen leading to the disease is uropathogenic Escherichia coli (UPEC). While many patients can handle the infection well and recover, severe and recurring infections are a common problem, especially in elderly, immunodeficient, or kidney transplanted patients. If a different response from the innate immune cells to a recurring infection can be the reason for a different course of PN has not yet been investigated. Fibrosis and collagen deposition are side effects during PN that impair kidney function. IL-22 is known to influence fibrosis, but its role for disease outcome during PN is unknown. During PN, kidney macrophages and recruited neutrophils act as a first line of defense against UPEC. After infection, macrophages can be replenished by clonal expansion or by infiltrating monocytes. The role of monocytes during acute PN and on recovery is unknown. Therefore, we aim to (I) elucidate the role of monocytes and study how macrophages are replenished after infection, (II) identify the role of IL-22 in kidney repair after PN and (III) determine the differences of the innate immune response of a first infection compared to recurring PN.