Innovative solutions are needed for the treatment of bacterial infections, and a range of antibacterial molecules have been explored as alternatives to antibiotics. A different approach is to investigate the immune system of the host for new ways of making the antibacterial defence more efficient. However, the immune system has a dual role as protector and cause of disease: in addition to being protective, increasing evidence shows that innate immune responses can become excessive and cause acute symptoms and tissue pathology during infection. This role of innate immunity in disease suggests that the immune system should be targeted therapeutically, to inhibit over-reactivity. The ultimate goal is to develop therapies that selectively attenuate destructive immune response cascades, while augmenting the protective antimicrobial defence but such treatment options have remained underexplored, owing to the molecular proximity of the protective and destructive effects of the immune response. The concept of innate immunomodulation therapy has been developed successfully in urinary tract infections, based on detailed studies of innate immune activation and disease pathogenesis. Effective, disease-specific, immunomodulatory strategies have been developed by targeting specific immune response regulators including key transcription factors. In acute pyelonephritis, targeting interferon regulatory factor 7 using small interfering RNA or treatment with antimicrobial peptide cathelicidin was protective and, in acute cystitis, targeting overactive effector molecules such as IL-1β, MMP7, COX2, cAMP and the pain-sensing receptor NK1R has been successful in vivo. Furthermore, other UTI treatment strategies, such as inhibiting bacterial adhesion and vaccination, have also shown promise.

治疗细菌感染需要创新的解决方案，并且已经探索了一系列抗菌分子作为抗生素的替代品。另一种方法是研究宿主的免疫系统，寻找使抗菌防御更有效的新方法。然而，免疫系统具有作为保护者和疾病原因的双重作用：除了具有保护作用外，越来越多的证据表明，先天免疫反应可能变得过度，并在感染期间引起急性症状和组织病理学。先天免疫在疾病中的这种作用表明，免疫系统应作为治疗目标，以抑制过度反应。最终目标是开发选择性减弱破坏性免疫反应级联反应的疗法，虽然增强了保护性抗菌防御，但由于免疫反应的保护和破坏作用的分子接近性，此类治疗方案仍未得到充分探索。基于对先天免疫激活和疾病发病机制的详细研究，先天免疫调节疗法的概念已在尿路感染中成功开发。通过靶向特定的免疫反应调节剂（包括关键转录因子）开发了有效的、疾病特异性的免疫调节策略。在急性肾盂肾炎中，使用小干扰 RNA 靶向干扰素调节因子 7 或用抗菌肽 cathelicidin 治疗具有保护作用，在急性膀胱炎中，靶向过度活跃的效应分子，如 IL-1β、MMP7、COX2、cAMP 和痛觉受体 NK1R 已在体内取得成功。此外，其他 UTI 治疗策略，如抑制细菌粘附和疫苗接种，也显示出前景。