TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads
TLR8 regulation of LILRA3 in monocytes is abrogated in human immunodeficiency virus infection and correlates to CD4 counts and virus loads
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DOI：
10.1186/s12977-016-0248-y
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发表时间：
2016-03-12
期刊：
影响因子：
3.3
通讯作者：
Witte, Torsten
中科院分区：
文献类型：
--
作者：
Low, Hui Zhi;Ahrenstorf, Gerrit;Witte, Torsten
背景：LILRA 3是一种免疫刺激分子，可条件性诱导细胞毒性细胞增殖。LILRA 3具有与多种免疫病症相关的缺失基因型。在这项研究中，我们想分析LILRA 3的调节及其意义的背景下，HIV infection.Results：我们分析了一组TLR激动剂，发现ssRNA 40，TLR 8激动剂，是一个有效的诱导剂LILRA 3在健康个体。然而，这种调节在艾滋病毒中大大减少。TLR 8与TLR 4对LILRA 3诱导的比较表明，在健康对照中，LPS诱导的LILRA 3比ssRNA 40少，但在HIV患者中则不然。LILRA 3诱导水平与未治疗患者的病毒载量和CD 4计数相关。重组LILRA 3可以诱导宿主的促炎基因，其中包括IL-6和IL-1 α，以及改变MHC和共刺激分子在单核细胞和B-cells.Conclusion的表达：我们的实验指向一个有益的作用LILRA 3在病毒感染，特别是在ssRNA病毒，如HIV，从事TLR 8。然而，LILRA 3的潜在有益作用在HIV感染期间被废除。我们认为，还需要做更多的工作来研究LILRA 3在感染性疾病中的作用，并且有可能探索LILRA 3在治疗病毒感染中的用途。
Background: LILRA3 is an immunostimulatory molecule which can conditionally induce the proliferation of cytotoxic cells. LILRA3 has a deletion genotype which is associated with multiple immune disorders. In this study, we wanted to analyze the regulation of LILRA3 and its significance in the context of HIV infection.Results: We analyzed a panel of TLR agonists and found that ssRNA40, a TLR8 agonist, is a potent inducer of LILRA3 in healthy individuals. However, this regulation is much diminished in HIV. Comparison of TLR8 to TLR4 induction of LILRA3 indicated that LPS induces less LILRA3 than ssRNA40 among healthy controls, but not HIV patients. Levels of LILRA3 induction correlated to virus load and CD4 counts in untreated patients. Recombinant LILRA3 can induce a host of proinflammatory genes which include IL-6 and IL-1 alpha, as well as alter the expression of MHC and costimulatory molecules in monocytes and B-cells.Conclusion: Our experiments point towards a beneficial role for LILRA3 in virus infections, especially in ssRNA viruses, like HIV, that engage TLR8. However, the potentially beneficial role of LILRA3 is abrogated during a HIV infection. We believe that more work has to be done to study the role of LILRA3 in infectious diseases and that there is a potential for exploring the use of LILRA3 in the treatment of virus infections.