Decreased Ficolin-3-mediated Complement Lectin Pathway Activation and Alternative Pathway Amplification During Bacterial Infections in Patients With Type 2 Diabetes Mellitus
Decreased Ficolin-3-mediated Complement Lectin Pathway Activation and Alternative Pathway Amplification During Bacterial Infections in Patients With Type 2 Diabetes Mellitus
复制标题
DOI：
10.3389/fimmu.2019.00509
复制
发表时间：
2019-03-20
影响因子：
7.3
通讯作者：
Hosszufalusi, Nora
中科院分区：
文献类型：
--
作者：
Barkai, Laszlo Jozsef;Sipter, Emese;Hosszufalusi, Nora
细菌感染在糖尿病患者中是常见和严重的。糖尿病本身是否会诱导补体系统的功能改变，从而在感染期间阻碍激活尚不清楚。我们研究了2型糖尿病（T2DM）患者细菌感染期间补体系统的关键要素，并将其与非糖尿病（ND）个体进行了比较。采用前瞻性设计，我们纳入了197名T2DM和196名ND受试者，所有受试者均临床诊断为急性社区获得性细菌感染。测定了ficolin-3介导的凝集素（F3-LP）、甘露糖结合凝集素介导的凝集素-(mll - lp)、经典途径（CP）和替代途径（AP）的功能活性，以及补体激活产物C4d和sC5b-9的浓度。T2DM患者F3-LP和AP的体外功能活性显著高于ND患者，（中位数分别为64%对45%，p = 0.0354和75对28%，p = 0.0013），表明T2DM患者体内F3-LP和AP的激活和消耗减少，而在T2DM和ND患者之间没有观察到CP和MBL-LP的功能能力差异。F3-LP和AP活性降低在尿路感染的糖尿病患者中最为明显，这些患者的微生物培养结果为大肠杆菌阳性。T2DM组3个月死亡率与F3-LP和AP降低显著相关，但与CP激活无关。T2DM患者的C4d和sC5b-9浓度明显低于ND患者。总之，与非糖尿病患者相比，我们发现2型糖尿病患者在细菌感染期间F3-LP激活受损，AP扩增缺乏，这表明补体介导的对2型糖尿病患者细菌感染的保护作用减弱。
Bacterial infections are frequent and severe in patients with diabetes mellitus. Whether diabetes per se induces functional alterations in the complement system hampering activation during infection is unknown. We investigated key elements of the complement system during bacterial infections in patients with type 2 diabetes mellitus (T2DM) and compared them to non-diabetic (ND) individuals. Using a prospective design, we included 197 T2DM, and 196 ND subjects, all with clinical diagnosis of acute community- acquired bacterial infections. Functional activities of the ficolin-3-mediated lectin (F3-LP), mannose binding lectin-mediated lectin-(MBL-LP), classical (CP), and alternative pathways (AP), as well as concentrations of complement activation products C4d and sC5b-9 were determined. Functional in vitro activities of F3-LP and AP were significantly higher in T2DM than in ND subjects, (median 64% vs. 45%, p = 0.0354 and 75 vs. 28%, p = 0.0013, respectively), indicating a decreased in vivo activation and lack of consumption of F3-LP and AP in T2DM patients, whereas no difference in functional capacities of CP and MBL-LP were observed between T2DM and ND subjects. Diminished F3-LP and AP activation was most pronounced in diabetic patients with urinary tract infections with positive microbiological culture results for Escherichia coli bacteria. In the T2DM group 3-months mortality significantly associated with diminished F3-LP and AP, but not with CP activation. Concentrations of C4d and sC5b-9 were significantly lower in the T2DM than in ND patients. In conclusion, we found impaired F3-LP activation and lack of AP amplification during bacterial infections in patients with type 2 diabetes, compared to non-diabetic subjects, suggesting a diminished complement mediated protection to bacterial infections in T2DM.