Role of myeloid immune cells in healing and recurrence of pyelonephritis

肾盂肾炎(PN)是一种肾脏感染，是尿路感染的并发症，从膀胱上升到肾脏。引起该病的主要病原体为尿路致病性大肠埃希菌(UPEC)。虽然许多患者可以很好地处理感染并康复，但严重和复发的感染是一个常见的问题，特别是在老年、免疫缺陷或肾移植患者中。如果先天免疫细胞对反复感染的反应不同可能是导致PN病程不同的原因，目前还没有进行研究。纤维化和胶原沉积是PN过程中损害肾功能的副作用。已知IL-22影响纤维化，但其在PN期间对疾病转归的作用尚不清楚。在PN期间，肾巨噬细胞和募集的中性粒细胞作为对抗UPEC的第一道防线。感染后，巨噬细胞可以通过克隆性扩增或单核细胞渗透来补充。单核细胞在急性PN期间和恢复过程中的作用尚不清楚。因此，我们的目标是(I)阐明单核细胞的作用并研究巨噬细胞在感染后如何补充；(Ii)确定IL-22在PN后肾脏修复中的作用；(Iii)确定首次感染与复发PN的先天免疫反应的差异。

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.