Low Hui Zhi, Ahrenstorf Gerrit, Pommerenke Claudia, Habermann Nadine, Schughart Klaus, Ordóñez David, Stripecke Renata, Wilk Esther, Witte Torsten
Department of Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Retrovirology. 2016 Mar 12;13:15. doi: 10.1186/s12977-016-0248-y.
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.
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-1α, as well as alter the expression of MHC and costimulatory molecules in monocytes and B-cells.
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.
LILRA3是一种免疫刺激分子，可条件性诱导细胞毒性细胞增殖。LILRA3具有一种与多种免疫紊乱相关的缺失基因型。在本研究中，我们希望分析LILRA3的调控及其在HIV感染背景下的意义。
我们分析了一组Toll样受体（TLR）激动剂，发现TLR8激动剂ssRNA40是健康个体中LILRA3的有效诱导剂。然而，在HIV感染中这种调控作用大大减弱。比较TLR8和TLR4对LILRA3的诱导作用表明，在健康对照中，脂多糖（LPS）诱导的LILRA3比ssRNA40少，但在HIV患者中并非如此。未治疗患者中LILRA3的诱导水平与病毒载量和CD4细胞计数相关。重组LILRA3可诱导一系列促炎基因，包括IL-6和IL-1α，还可改变单核细胞和B细胞中主要组织相容性复合体（MHC）和共刺激分子的表达。
我们的实验表明LILRA3在病毒感染中具有有益作用，尤其是在像HIV这样可激活TLR8的单链RNA病毒感染中。然而，在HIV感染期间LILRA3的潜在有益作用被消除。我们认为有必要开展更多工作来研究LILRA3在传染病中的作用，并且探索将LILRA3用于治疗病毒感染具有潜力。
