The NLRP3 Inflammasome Is Upregulated in HIV-Infected Antiretroviral Therapy-Treated Individuals with Defective Immune Recovery.
The NLRP3 Inflammasome Is Upregulated in HIV-Infected Antiretroviral Therapy-Treated Individuals with Defective Immune Recovery.
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DOI：
10.3389/fimmu.2018.00214
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发表时间：
2018
影响因子：
7.3
通讯作者：
Trabattoni D
中科院分区：
文献类型：
--
作者：
Bandera A;Masetti M;Fabbiani M;Biasin M;Muscatello A;Squillace N;Clerici M;Gori A;Trabattoni D
炎症小体介导的caspase-1激活调节炎症反应和下垂。我们分析了HIV感染抗逆转录病毒疗法(ART)治疗的患者中炎症体相关基因和免疫重建之间的可能联系。横断面病例对照研究。HIV感染者接受抗逆转录病毒治疗24个月，≥-RNA50个/毫升，持续12个 月，如果≥计数为CD4500或CD4350 /≥L，则分别定义为免疫应答者(IR)和无应答者(INR)。检测炎症体基因caspase1、3、4、5和γ干扰素诱导蛋白16(IFI16)在未刺激和脂多糖或羟甲硫醇-2处理的HIV-1BaL病毒粒子刺激的外周血单核细胞中的表达。对微生物易位标志物进行评估。共纳入39例患者(IRS 22例，INRS 17例)。内毒素刺激的炎症体基因在INRS中显著上调。而HIV-1BaL刺激诱导的(NOD)样受体(NLR)家族3(NLRP3)在IR和INRS中的表达，INRS的NLRP3和IL-18的表达明显高于IR。Caspase-1在两组中的表达也显著高于对照组，而caspase 3、4和5在两组中的表达相似。两组微生物易位标志物(内毒素和可溶性CD14)差异无统计学意义。INR患者NLRP3和caspase-1表达上调。这可能在持久的免疫激活中发挥作用，这是INRS的特征。Caspase-1上调可通过上睑下垂导致CD4T细胞丢失，导致CD4T细胞恢复不理想。
Inflammasome-mediated activation of caspase-1 regulates inflammatory responses and pyroptosis. We analyzed possible associations between inflammasome-related genes and immune reconstitution in HIV-infected antiretroviral therapy (ART)-treated patients. Cross-sectional, case–control study. HIV-infected patients on ART for ≥24 months with HIV-RNA<50 cp/mL for ≥12 months were enrolled and defined as immunological responders (IR) or non-responders (INR) if CD4 count was ≥500 or ≤350 cells/μL, respectively. Expression of inflammasome genes, caspases 1, 3, 4, 5 and γ-interferon-inducible protein 16 (IFI16) was measured in unstimulated and LPS- or aldrithiol-2-treated HIV-1BaL virions-stimulated peripheral blood mononuclear cells. Microbial translocation markers were evaluated. Thirty-nine patients (22 IRs; 17 INRs) were enrolled. LPS-stimulated inflammasome genes were significantly upregulated in INRs. Whereas HIV-1BaL stimulation induced (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) expression in both IRs and INRs, NLRP3 and IL-18 expression was significantly increased in INRs compared to IRs. Significant higher caspase-1 expression was seen as well, whereas caspase 3, 4, and 5 expression was similar in both groups. No differences in microbial translocation markers (LPS and soluble CD14) were detected in the two groups. Upregulation of NLRP3 and caspase-1 is observed in INR patients. This could play a role in persistent immune activation that characterize INRs. Caspase-1 upregulation could induce CD4 T-cell loss via pyroptosis, contributing to unsatisfactory CD4 T-cells recovery.
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DOI：
10.1097/qai.0000000000001080
发表时间：
2016-10-01
影响因子：
3.6
作者：
Stiksrud, Birgitte;Lorvik, Kristina Berg;Dyrhol-Riise, Anne M.
通讯作者：
Dyrhol-Riise, Anne M.
影响因子：
2.2
作者：
Tincati C;Douek DC;Marchetti G
通讯作者：
Marchetti G
影响因子：
4.4
作者：
Hitzler, Iris;Sayi, Ayca;Mueller, Anne
通讯作者：
Mueller, Anne
DOI：
10.1073/pnas.1609057113
发表时间：
2016-08-02
影响因子：
11.1
作者：
Imamichi, Hiromi;Dewar, Robin L.;Lane, H. Clifford
通讯作者：
Lane, H. Clifford
影响因子：
6.4
作者：
Hunt, PW;Martin, JN;Deeks, SG
通讯作者：
Deeks, SG