急性和慢性乙型肝炎患者NLRP3，AIM2和IFI16炎性体的差异激活。

StephenW

Viral Immunol. 2018 Sep 15. doi: 10.1089/vim.2018.0058. [Epub ahead of print]
Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B.
Chen H1,2, He G3, Chen Y3, Zhang X4, Wu S1.
Author information

1
    1 Department of Infectious Diseases, The Second Clinical Medical College, Jinan University , Shenzhen, China .
2
    2 Key Laboratory of Pathogenic Microorganism of Shenzhen , Shenzhen, China .
3
    3 Department of Clinical Laboratory, The Second Clinical Medical College, Jinan University , Shenzhen, China .
4
    4 Hepatology Unit and Key Laboratory for Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University , Guangzhou, China .

Abstract

Nod-like receptor protein 3 (NLRP3), absent in melanoma 2 (AIM2), and interferon gamma inducible protein 16 (IFI16) are innate immune sensors for intracellular microbes, which can be activated by various dangerous signals and subsequently lead to caspase-1 (CASP1) activation and the maturation cleavage of effector molecules pro-IL-1β and pro-IL-18. Their roles in immunopathology of acute and chronic hepatitis B virus (HBV) infection are still unclear. In this study, we first investigated the activation of NLRP3, AIM2, and IFI16 inflammasomes in peripheral blood mononuclear cells (PBMCs) from patients infected with acute hepatitis B (AHB) and chronic hepatitis B (CHB) by quantitative real-time PCR and enzyme-linked immunosorbent assay. We next analyzed the impact of hepatitis B e antigen (HBeAg) on activation of AIM2 and IFI16 inflammasomes in PBMCs of CHB patients stimulated in vitro with AIM2 and IFI16 agonist ligands, poly (dA:dT) and VACA-70mer, respectively. The results showed that the mRNA expression levels of AIM2, IFI16, and CASP1 in PBMCs from AHB and CHB patients were both upregulated. Furthermore, the mRNA levels of AIM2 and IFI16 in CHB patients were significantly positively correlated with serum HBV loads. However, only in patients with AHB there was elevation of serum IL-1β and IL-18. There was no activation of NLRP3, AIM2, and IFI16 inflammasomes in CHB patients. Stimulation of PBMCs of CHB patients in vitro with poly (dA:dT) and VACA-70mer induced the activation of AIM2 and IFI16 inflammasomes, respectively. This ligand-induced activation was suppressed by HBeAg. Our results suggest that there exists activation of the AIM2 and IFI16 inflammasomes, but not the NLRP3 inflammasome, in AHB, and the activation of the AIM2 and IFI16 inflammasomes can be inhibited by HBeAg in CHB, which may contribute to HBV-induced immunotolerance.
KEYWORDS:

AIM2; HBV; IFI16; NLRP3; inflammasome

PMID:
    30222506
DOI:
    10.1089/vim.2018.0058

StephenW

病毒免疫。 2018年9月15日。土井：10.1089 / vim.2018.0058。 [提前打印]
急性和慢性乙型肝炎患者NLRP3，AIM2和IFI16炎性体的差异激活。
陈H1,2，何G3，陈Y3，张X4，吴S1。
作者信息

1
    1暨南大学第二临床医学院传染病科，深圳
2
    2深圳市深圳市病原微生物重点实验室
3
    3暨南大学第二临床医学院临床实验室，深圳
4
    4南方医科大学南方医院感染科，肝脏病科及器官衰竭研究重点实验室，广州

抽象

在黑色素瘤2（AIM2）和干扰素γ诱导蛋白16（IFI16）中不存在的Nod样受体蛋白3（NLRP3）是细胞内微生物的先天免疫传感器，其可被各种危险信号激活并随后导致caspase-1 （CASP1）活化和效应分子pro-IL-1β和pro-IL-18的成熟切割。他们在急性和慢性乙型肝炎病毒（HBV）感染的免疫病理学中的作用仍不清楚。在这项研究中，我们首先通过定量实时PCR和酶研究了感染急性乙型肝炎（AHB）和慢性乙型肝炎（CHB）的患者外周血单个核细胞（PBMCs）中NLRP3，AIM2和IFI16炎性体的激活。相关免疫吸附试验。我们接下来分析了乙型肝炎e抗原（HBeAg）对体外用AIM2和IFI16激动剂配体，poly（dA：dT）和VACA-70mer体外刺激的CHB患者的PBMC中AIM2和IFI16炎性体激活的影响。结果显示，AHB和CHB患者外周血单个核细胞中AIM2，IFI16和CASP1的mRNA表达水平均上调。此外，CHB患者AIM2和IFI16的mRNA水平与血清​​HBV负荷显着正相关。然而，仅在AHB患者中血清IL-1β和IL-18升高。在CHB患者中没有激活NLRP3，AIM2和IFI16炎性体。体外用聚（dA：dT）和VACA-70mer刺激CHB患者的PBMC诱导AIM2和IFI16炎性体的活化。 HBeAg抑制了配体诱导的激活。我们的研究结果表明，在AHB中存在AIM2和IFI16炎性体的激活而非NLRP3炎性体的激活，并且CHB中的HBeAg可以抑制AIM2和IFI16炎性体的激活，这可能有助于HBV诱导的免疫耐受。
关键词：

AIM2; HBV; IFI16; NLRP3;炎性

结论：
    30222506
DOI：
    10.1089 / vim.2018.0058