Evaluating and targeting C5a receptor in pyelonephritis

由大肠杆菌引起的尿路感染(UTI)是一种常见的传染病。这在妇女和儿童中尤其常见，对于糖尿病和肾移植患者来说是一个特别的问题。虽然抗生素可以用来治疗这种疾病，但频繁的复发或持续感染仍然是一个大问题。为了改进目前的治疗方法，需要更好地了解细菌如何能够入侵、生存和在尿路中生长，以及它们导致组织损伤的手段(S)。体内产生的炎症介质在宿主抵抗病原体的第一道防线中起着至关重要的作用；然而，当它们过度存在或调节失调时，也会造成伤害。C5a是一种强有力的炎症介质，已被证明与多种炎症和感染性疾病有关。这项拟议的研究旨在找出C5a是否以及如何参与肾脏和膀胱感染的发展，并有助于感染的复发或持续。如果我们成功地揭示了C5a如何作用于尿路组织中不同类型的细胞，促进细菌的入侵、存活和生长，这可能为阻断C5a的作用从而预防和治疗尿路感染提供有价值的手段。

Urinary tract infection (UTI) caused by the microbe E. coli is a common infectious disease. It is especially frequent in women and children and is a particular problem for patients with diabetes and renal transplants. Although antibiotics can be used to treat the disease, frequent recurrence or persistence of infection is still a big problem. A better understanding of how bacteria are able to invade, survive and grow in the urinary tract, and the mean(s) by which they cause tissue damage is required for improving current treatment. The inflammatory mediators generated in our body in response to infection play essential roles in the first line of host defense against pathogens; however, they can also cause harm when present in excess or are dysregulated. C5a is a potent inflammatory mediator which has been shown to be associated with various inflammatory and infectious diseases. The proposed research is to work out if and how C5a could participate in the development of kidney and bladder infection and contribute to the recurrence or persistence of infection. If we are successful in showing how C5a acts on different cell types within the urinary tract tissues to promote bacteria invasion, survival and growth, this may offer a valuable means to block the action of C5a and thus prevent and treat UTI.