NLRP3在乙型肝炎病毒感染中的研究进展

马 小雨, 梁 雅慧, 李 丽
陕西省延安大学附属医院 陕西延安 716000

摘要

目的：固有免疫系统是宿主抵御内外源性损伤的第一道防线，NLRP3 炎症小体作为固有免疫系统的关键成分，通过促进炎症因子分泌及细胞焦亡参与损伤的发生 [1]。乙型肝炎病毒（HBV）感染后由 Kupffer 细胞识别并产生 IL-1β和 IL-18 等炎症因子参与肝损伤的发生发展。以往研究认为，机体特异性免疫应答是 HBV 感染后介导肝脏免疫性损伤的关键。然而，越来越多的研究发现固有免疫系统在 HBV 感染过程中同样具有重要作用。NLRP3 炎性小体在 HBV 感染所致疾病中均发挥了巨大作用[2]。以下将通过综述国内外文献来介绍 NLRP3 炎性小体在 HBV 感染所致疾病中的研究进展。

参考

[1]STIENSTRAR，TACK CJ，KANNEGANTI TD，et al．The inflam-masome puts obesity in the danger zone[J]．Cell Metab，2012，15（1）：10-18． [2]Bae J Y，Lee S W，Shin Y H，et al. P2X7 receptor and NLRP3 inflam-masome activation in head and neck cancer [J]. Oncotarget，2017，8（30）：48972-48982. [3]WANG W，XIAO F，WAN P，et al． EV71 3D protein binds withNLＲP3 and enhances the assembly of inflammasome complex[J]． PLoS Pathog，2017，13（1）：e1006123． [4]Schroder K，Sagulenko V，Zamoshnikova A，et al. Acute lipo-polysaccharide priming boosts inflammasome activation independently of inflammasome sensor induction [J]. Immunobiology，2012，217（12）：1325-1329. [5]Kahlenberg J M，Dubyak G R． Mechanisms of caspase-1 activationby P2X7 receptor-mediated K+release[J]． Am J Physiol CellPhysiol，2004，286（5）：C1100 -C1108． [6]Ding，J.，Wang，K.，Liu，W. et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature 535，111 116（2016）. https：//doi.org/10.1038/nature18590 [7]Bauernfeind F.G.，Horvath G.，Stutz A.，Alnemri E.S.，MacDonald K.，Speert D.，Fernandes-Alnemri T.，Wu J.，Monks B.G.，Fitzgerald K.A.，et al. Cutting Edge：NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression. J. Immunol. 2009；183：787 791. doi：10.4049/jimmunol.0901363. [8]Franchi L.，Eigenbrod T.，Núñez G. Cutting Edge：TNF-α Mediates Sensitization to ATP and Silica via the NLRP3 Inflammasome in the Absence of Microbial Stimulation. J. Immunol. 2009；183：792 796. doi：10.4049/jimmunol.0900173. [9]WHO. Hepatitis B. http：//www.who.int/mediacentre/factsheets/fs204/en/. AccessedJuly 2022 [8]Vajjhala P.R.，Mirams R.E.，Hill J.M. Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein. J. Biol. Chem. 2012；287：41732 41743. doi：10.1074/jbc.M112.381228. 9Duncan J.A.，Bergstralh D.T.，Wang Y.，Willingham S.B.，Ye Z.，Zimmermann A.G.，Ting J.P.-Y. Cryopyrin/NALP3 binds ATP/dATP，is an ATPase，and requires ATP binding to mediate inflammatory signaling. Proc. Natl. Acad. Sci. USA. 2007；104：8041 8046. doi：10.1073/pnas.0611496104. [10]Yu X，Lan P，Hou X，Han Q，Lu N，Li T，Jiao C，Zhang J，Zhang C，Tian Z. HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing the NF-κB pathway and ROS production. J Hepatol. 2017 Apr；66（4）：693-702. doi：0.1016/j.jhep.2016.12.018. Epub 2016 Dec 24. PMID：28027970. [11]Al-Mahtab M，Akbar SM，Aguilar JC，Uddin MH，Khan MS，Rahman S. Therapeutic potential of a combined hepatitis B virus surface and core antigen vaccine in patients with chronic hepatitis B. Hepatol Int. 2013 Oct；7（4）：981-9. doi：10.1007/s12072-013-9486-4. Epub 2013 Nov 9. PMID：26202028. [12]Ding X，Lei Q，Li T，Li L，Qin B. Hepatitis B core antigen can regulate NLRP3 inflammasome pathway in HepG2 cells. J Med Virol. 2019 Aug；91（8）：1528-1536. doi：10.1002/jmv.25490. Epub 2019 May 16. PMID：31017673.