Division of Nephrology, Department of Internal Medicine, Renal Transplant Unit, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Immun Inflamm Dis. 2020 Mar;8(1):80-92. doi: 10.1002/iid3.287. Epub 2020 Feb 7.
Urinary tract infection recurrence is common, particularly in women and immunocompromised patients, such as renal transplant recipients (RTRs). Mucosal-associated invariant T (MAIT) cells play a role in the antibacterial response by recognizing bacterial riboflavin metabolites produced by bacteria such as Escherichia coli. Here, we investigated whether MAIT cells are involved in the pathogenesis of recurrent urinary tract infections (RUTIs).
Using multichannel flow cytometry, we characterized the MAIT cell phenotype and function in blood from immunocompetent adults with (n = 13) and without RUTIs (n = 10) and in RTRs with (n = 9) and without RUTIs (n = 10).
There were no differences in the numbers of MAIT cells between the study groups. MAIT cells in patients with RUTI expressed T-bet more often than those in controls. MAIT cells from immunocompetent RUTI participants required more antigen-presenting cells coincubated with E. coli to evoke a similar cytokine and degranulation response than those from controls. This effect was absent in the RTR with RUTI vs RTR control groups, where the overall percentage of MAIT cells that responded to stimulation was already reduced.
Circulating MAIT cells in immunocompetent individuals with RUTIs respond to bacterial stimuli with reduced efficacy, which suggests that they are involved in the pathogenesis of RUTIs.
尿路感染复发很常见,尤其是在女性和免疫功能低下的患者中,如肾移植受者(RTR)。黏膜相关不变 T(MAIT)细胞通过识别细菌如大肠杆菌产生的细菌核糖核酸代谢物,在抗菌反应中发挥作用。在这里,我们研究了 MAIT 细胞是否参与复发性尿路感染(RUTI)的发病机制。
使用多通道流式细胞术,我们描述了免疫功能正常的成年人(n=13)和无 RUTI(n=10)以及有 RUTI(n=9)和无 RUTI(n=10)的 RTR 血液中的 MAIT 细胞表型和功能。
研究组之间 MAIT 细胞的数量没有差异。患有 RUTI 的患者的 MAIT 细胞比对照组更频繁地表达 T-bet。与对照组相比,来自免疫功能正常的 RUTI 参与者的 MAIT 细胞需要更多与大肠杆菌共培养的抗原呈递细胞才能引起类似的细胞因子和脱颗粒反应。在 RTR 与 RTR 对照组中,这种效应是不存在的,因为 MAIT 细胞对刺激的总体反应百分比已经降低。
免疫功能正常的 RUTI 个体循环中的 MAIT 细胞对细菌刺激的反应效率降低,这表明它们参与了 RUTI 的发病机制。