Godaly Gabriela, Ambite Ines, Puthia Manoj, Nadeem Aftab, Ho James, Nagy Karoly, Huang Yujing, Rydström Gustav, Svanborg Catharina
Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, 221 00 Lund, Sweden.
Pathogens. 2016 Feb 24;5(1):24. doi: 10.3390/pathogens5010024.
Rapid developments in infection biology create new and exciting options for individualized diagnostics and therapy. Such new practices are needed to improve patient survival and reduce morbidity. Molecular determinants of host resistance to infection are being characterized, making it possible to identify susceptible individuals and to predict their risk for future morbidity. Immunotherapy is emerging as a new strategy to treat infections worldwide and controlled boosting of the host immune defense represents an important therapeutic alternative to antibiotics. In proof of concept studies, we have demonstrated that this approach is feasible. The long-term goal is not just to remove the pathogens but to also develop technologies that restore resistance to infection in disease-prone patients and devise personalized therapeutic interventions. Here, we discuss some approaches to reaching these goals, in patients with urinary tract infection (UTI). We describe critical host signaling pathways that define symptoms and pathology and the genetic control of innate immune responses that balance protection against tissue damage. For some of these genes, human relevance has been documented in clinical studies, identifying them as potential targets for immune-modulatory therapies, as a complement to antibiotics.
感染生物学的快速发展为个性化诊断和治疗带来了新的、令人兴奋的选择。需要这些新方法来提高患者生存率并降低发病率。宿主对感染的抵抗力的分子决定因素正在被阐明,这使得识别易感个体并预测他们未来发病的风险成为可能。免疫疗法正在成为一种治疗全球感染的新策略,而对宿主免疫防御进行可控增强是抗生素的一种重要治疗替代方法。在概念验证研究中,我们已经证明这种方法是可行的。长期目标不仅是清除病原体,还要开发能够恢复易患疾病患者对感染的抵抗力的技术,并设计个性化的治疗干预措施。在此,我们讨论在患有尿路感染(UTI)的患者中实现这些目标的一些方法。我们描述了定义症状和病理的关键宿主信号通路以及平衡对组织损伤的保护的先天免疫反应的遗传控制。对于其中一些基因,临床研究已经证明了其与人类的相关性,将它们确定为免疫调节疗法的潜在靶点,作为抗生素的补充。