Healing / recurrence

SP6: Role of myeloid immune cells in healing and recurrence of pyelonephritis

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. The cytokine interleukin-22 (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, the aim is to elucidate the role of monocytes and study how macrophages are replenished after infection, to identify the role of IL-22 in kidney repair after PN and to determine the differences of the innate immune response of a first infection compared to recurring PN.
Serial intravital microscopy is presently the only technique that can track renal cells, immune cell migration and bacteria with high spatial and temporal resolution in vivo. With 2p-IVM we will gain new insights into the dynamics of basic mechanisms and factors that are involved in the regeneration of the kidney that will help to address the need for new therapeutic targets.