Vierbuchen Tim, Bang Corinna, Rosigkeit Hanna, Schmitz Ruth A, Heine Holger
Division of Innate Immunity, Research Center Borstel, Borstel, Germany.
Institute for General Microbiology, Christian-Albrechts-University Kiel, Kiel, Germany.
Front Immunol. 2017 Nov 13;8:1535. doi: 10.3389/fimmu.2017.01535. eCollection 2017.
The archaeon is a member of the gut microbiota; yet, the molecular cross-talk between archaea and the human immune system and its potential contribution to inflammatory diseases has not been evaluated. Although archaea are as bacteria prokaryotes, they form a distinct domain having unique features such as different cell wall structures and membrane lipids. So far, no microbe-associated molecular patterns of archaea which activate innate immune receptors have been identified. By stimulating human myeloid cells with and purified archaeal nucleic acids, we identified both the microorganism and its RNA as potent stimuli for the innate immune system. To dissect the recognition and activation pathways induced by , human monocytic BLaER1 knockout cells were generated using the CRISPR/Cas9 system targeting components of TLR and inflammasome signaling. While the recognition of is mediated by TLR7 and TLR8, activation of the NLRP3 inflammasome depends solely on TLR8 engagement. Notably, this process resembles hallmarks of both the canonical and the recently described alternative inflammasome activation. Thus, we have demonstrated for the first time the specific recognition of and response to an archaeon by human cells at the molecular level.
古菌是肠道微生物群的成员；然而，古菌与人类免疫系统之间的分子相互作用及其对炎症性疾病的潜在影响尚未得到评估。尽管古菌与细菌一样都是原核生物，但它们形成了一个独特的域，具有独特的特征，如不同的细胞壁结构和膜脂。到目前为止，尚未鉴定出激活先天免疫受体的古菌微生物相关分子模式。通过用纯化的古菌核酸刺激人髓细胞，我们确定了该微生物及其RNA都是先天免疫系统的有效刺激物。为了剖析由该微生物诱导的识别和激活途径，使用靶向TLR和炎性小体信号传导成分的CRISPR/Cas9系统生成了人单核细胞BLaER1敲除细胞。虽然对该微生物的识别由TLR7和TLR8介导，但NLRP3炎性小体的激活仅取决于TLR8的参与。值得注意的是，这一过程类似于经典炎性小体激活和最近描述的替代性炎性小体激活的特征。因此，我们首次在分子水平上证明了人类细胞对古菌的特异性识别和反应。
