Infectious Diseases and Immunity, Imperial College London, The Commonwealth Building, Du Cane Road, London W12 0NN, UK.
Institute of Medical Microbiology and Hygiene, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Nat Rev Urol. 2017 May;14(5):284-295. doi: 10.1038/nrurol.2017.25. Epub 2017 Mar 7.
Urinary tract infections (UTIs) cause a huge burden of morbidity worldwide with recurrent UTIs becoming increasingly frequent owing to the emergence of antibiotic-resistant bacterial strains. Interactions between the innate and adaptive immune responses to pathogens colonizing the urinary tract have been the focus of much research. Inflammasomes are part of the innate immune defence and can respond rapidly to infectious insult. Assembly of the multiprotein inflammasome complex activates caspase-1, processes proinflammatory cytokines IL-1β and IL-18, and induces pyroptosis. These effector pathways, in turn, act at different levels to either prevent or resolve infection, or eliminate the infectious agent itself. In certain instances, inflammasome activation promotes tissue pathology; however, the precise functions of inflammasomes in UTIs remain unexplored. An improved understanding of inflammasomes could provide novel approaches for the design of diagnostics and therapeutics for complicated UTIs, enabling us to overcome the challenge of drug resistance.
尿路感染(UTI)在全球范围内造成了巨大的发病负担,由于抗生素耐药菌株的出现,复发性 UTI 变得越来越频繁。定植于泌尿道的病原体引起的固有免疫和适应性免疫反应之间的相互作用一直是许多研究的重点。炎性小体是固有免疫防御的一部分,可以对感染性损伤迅速作出反应。多蛋白炎性小体复合物的组装激活半胱天冬酶-1,处理促炎细胞因子 IL-1β和 IL-18,并诱导细胞焦亡。这些效应途径反过来在不同水平上发挥作用,以防止或解决感染,或消除感染因子本身。在某些情况下,炎性小体的激活会促进组织病理学;然而,炎性小体在 UTI 中的确切功能仍未被探索。对炎性小体的深入了解可以为设计复杂 UTI 的诊断和治疗方法提供新的途径,使我们能够克服耐药性的挑战。