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Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B.
Viral Immunol 2018; 31(9):639-645VI

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30222506

Citation

Chen, Hongtao, et al. "Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans With Acute and Chronic Hepatitis B." Viral Immunology, vol. 31, no. 9, 2018, pp. 639-645.
Chen H, He G, Chen Y, et al. Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B. Viral Immunol. 2018;31(9):639-645.
Chen, H., He, G., Chen, Y., Zhang, X., & Wu, S. (2018). Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B. Viral Immunology, 31(9), pp. 639-645. doi:10.1089/vim.2018.0058.
Chen H, et al. Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans With Acute and Chronic Hepatitis B. Viral Immunol. 2018;31(9):639-645. PubMed PMID: 30222506.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B. AU - Chen,Hongtao, AU - He,Guirong, AU - Chen,Yue, AU - Zhang,Xiaoyong, AU - Wu,Shipin, Y1 - 2018/09/15/ PY - 2018/9/18/pubmed PY - 2018/12/21/medline PY - 2018/9/18/entrez KW - AIM2 KW - HBV KW - IFI16 KW - NLRP3 KW - inflammasome SP - 639 EP - 645 JF - Viral immunology JO - Viral Immunol. VL - 31 IS - 9 N2 - 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. SN - 1557-8976 UR - https://www.unboundmedicine.com/medline/citation/30222506/Differential_Activation_of_NLRP3_AIM2_and_IFI16_Inflammasomes_in_Humans_with_Acute_and_Chronic_Hepatitis_B_ L2 - https://www.liebertpub.com/doi/full/10.1089/vim.2018.0058?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -