Triggers of NLRC4 and AIM2 inflammasomes induce porcine IL-1β secretion
Triggers of NLRC4 and AIM2 inflammasomes induce porcine IL-1β secretion
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DOI：
10.1007/s11259-018-9729-x
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发表时间：
2018-12-01
影响因子：
2.2
通讯作者：
Lee, Geun-Shik
中科院分区：
文献类型：
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作者：
Ahn, Huijeong;Kim, Jeongeun;Lee, Geun-Shik
猪是一种重要的家畜，由于与人类在生理和解剖学上的相似性，猪可以作为大型动物模型。因此，猪免疫系统的组分如炎性小体需要表征用于疾病控制、疫苗接种和转化研究目的。以前，我们和其他人阐明了猪核苷酸结合寡聚化结构域（NOD）样受体（NLR）家族含Pyrin结构域3（NLRP 3）炎性小体激活。然而，到目前为止，猪NLR家族胱天蛋白酶募集结构域（CARD）-含有4（NLRC 4）和缺乏黑色素瘤2（AIM 2）炎性小体尚未得到很好的研究。在这项研究中，我们将明确定义的NLRC 4和AIM 2炎性小体触发物处理至猪外周血单核细胞（PBMC）和鼠骨髓衍生的巨噬细胞（BMDM），并观察白细胞介素（IL）-1 β成熟作为炎性小体激活的读数。NLRC 4（鞭毛蛋白）和AIM 2（dsDNA）触发剂导致猪PBMC和小鼠巨噬细胞中的IL-1 β分泌。此外，猪和小鼠NLRC 4和AIM 2炎性小体对NLRP 3抑制剂的反应不同。细菌性炎性体触发物，沙门氏菌、鼠伤寒血清型、单核细胞增生李斯特菌和大肠杆菌也诱导猪PBMC中的IL-1 β分泌。总之，我们认为小鼠中NLRC 4和AIM 2炎性小体的已知触发因子诱导猪PBMC中的IL-1 β分泌。
Pigs are an important livestock and serve as a large animal model due to physiological and anatomical similarities with humans. Thus, components of the porcine immune system such as inflammasomes need to be characterized for disease control, vaccination, and translational research purposes. Previously, we and others elucidated porcine nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family Pyrin domain containing 3 (NLRP3) inflammasome activation. However, until now, porcine NLR family caspase recruitment domain (CARD)-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inflammasomes have been not well studied. In this study, we treated well defined NLRC4 and AIM2 inflammasome triggers to porcine peripheral blood mononuclear cells (PBMCs) and murine bone-marrow derived macrophages (BMDMs) and observed interleukin (IL)-1 beta maturation as a readout of inflammasome activation. NLRC4 (flagellin) and AIM2 (dsDNA) triggers led to IL-1 beta secretion in both porcine PBMCs and mice macrophages. In addition, porcine and mouse NLRC4 and AIM2 inflammasomes responded differently to NLRP3 inhibitors. Bacterial inflammasome triggers, Salmonella enterica serovar Typhimurium, Listeria monocytogenes, and Escherichia coli, also induced IL-1 beta secretion in porcine PBMCs. Taken together, we suggest that known triggers of NLRC4 and AIM2 inflammasomes in mice induce IL-1 beta secretion in porcine PBMCs.