明矾激活牛NLRP3炎性小体。

Alum Activates the Bovine NLRP3 Inflammasome.

作者信息

Harte Ciaran, Gorman Aoife L, McCluskey S, Carty Michael, Bowie Andrew G, Scott C J, Meade Kieran G, Lavelle Ed C

机构信息

Adjuvant Research Group, School of Biochemistry and Immunology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.

Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre, Teagasc, Grange, Ireland.

出版信息

Front Immunol. 2017 Nov 9;8:1494. doi: 10.3389/fimmu.2017.01494. eCollection 2017.

Abstract

There has been a move away from vaccines composed of whole or inactivated antigens toward subunit-based vaccines, which although safe, provide less immunological protection. As a result, the use of adjuvants to enhance and direct adaptive immune responses has become the focus of much targeted bovine vaccine research. However, the mechanisms by which adjuvants work to enhance immunological protection in many cases remains unclear, although this knowledge is critical to the rational design of effective next generation vaccines. This study aimed to investigate the mechanisms by which alum, a commonly used adjuvant in bovine vaccines, enhances IL-1β secretion in bovine peripheral blood mononuclear cells (PBMCs). Unlike the case with human PBMCs, alum promoted IL-1β secretion in a subset of bovine PBMCs without priming with a toll-like receptor agonist. This suggests that PBMCs from some cattle are primed to produce this potent inflammatory cytokine and western blotting confirmed the presence of preexisting pro-IL-1β in PBMCs from a subset of 8-month-old cattle. To address the mechanism underlying alum-induced IL-1β secretion, specific inhibitors identified that alum mediates lysosomal disruption which subsequently activates the assembly of an NLRP3, ASC, caspase-1, and potentially caspase-8 containing complex. These components form an inflammasome, which mediates alum-induced IL-1β secretion in bovine PBMCs. Given the demonstrated role of the NLRP3 inflammasome in regulating adaptive immunity in murine systems, these results will inform further targeted research into the potential of inflammasome activation for rational vaccine design in cattle.

摘要

疫苗已从由完整或灭活抗原组成的疫苗转向基于亚单位的疫苗,后者虽然安全,但提供的免疫保护较少。因此,使用佐剂来增强和引导适应性免疫反应已成为许多针对性牛疫苗研究的重点。然而,尽管这一知识对于有效下一代疫苗的合理设计至关重要,但在许多情况下,佐剂增强免疫保护的机制仍不清楚。本研究旨在探讨牛疫苗中常用佐剂明矾增强牛外周血单核细胞(PBMCs)中IL-1β分泌的机制。与人类PBMCs不同,明矾在未用Toll样受体激动剂预刺激的情况下,促进了一部分牛PBMCs中IL-1β的分泌。这表明来自一些牛的PBMCs已被预刺激以产生这种强效炎性细胞因子,蛋白质印迹法证实了在一部分8月龄牛的PBMCs中存在预先存在的前体IL-1β。为了探讨明矾诱导IL-1β分泌的潜在机制,特异性抑制剂表明明矾介导溶酶体破坏,随后激活包含NLRP3、ASC、半胱天冬酶-1以及可能还有半胱天冬酶-8的复合物的组装。这些成分形成炎性小体,介导明矾诱导的牛PBMCs中IL-1β的分泌。鉴于NLRP3炎性小体在调节小鼠系统中的适应性免疫方面已得到证实的作用,这些结果将为进一步针对性研究炎性小体激活在牛合理疫苗设计中的潜力提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac2/5701618/fc68d7b43110/fimmu-08-01494-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索