Johns Colleen Elsa, Galam Lakshmi
Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Cell Biochem Biophys. 2022 Jun;80(2):295-299. doi: 10.1007/s12013-021-01056-y. Epub 2022 Feb 18.
Scientists recently made a significant breakthrough in the recognition of pathogens via guanylate binding protein 1 (GBP1). Wandel et al. [1] in Nature Immunology described their findings where GBP1 acts as a pattern recognition receptor that directly connects to lipopolysaccharide (LPS). GBP1 identifies gram-negative bacteria such as the enteric pathogen, Salmonella enterica serovar Typhimurium, that enter the cytoplasm of the host cell. GBP1 then quickly connects to LPS and stimulates the assembly of more GBPs in the order of GBP2, GBP3, and GBP4. Subsequently, inflammatory caspase-4 arrives at the GBP1-4 activation platform. Next, the activated caspase-4 drives the cleavage of Gasdermin D, triggering the release of the pro-inflammatory cytokine, interleukin-18 (IL-18) leading to inflammatory pyroptosis and cell death. Not only do these remarkable results expand our current understanding of GBP1, but they also carry the potential to develop therapeutic targets for inflammasome-mediated human disorders.
科学家们最近在通过鸟苷酸结合蛋白1（GBP1）识别病原体方面取得了重大突破。万德尔等人[1]在《自然免疫学》杂志上描述了他们的研究结果，即GBP1作为一种模式识别受体，直接与脂多糖（LPS）相连。GBP1能够识别革兰氏阴性菌，如肠道病原体鼠伤寒沙门氏菌，这些细菌会进入宿主细胞的细胞质。GBP1随后迅速与LPS相连，并刺激更多GBP按照GBP2、GBP3和GBP4的顺序组装。随后，炎性半胱天冬酶-4到达GBP1-4激活平台。接下来，活化的半胱天冬酶-4驱动Gasdermin D的切割，触发促炎细胞因子白细胞介素-18（IL-18）的释放，导致炎性细胞焦亡和细胞死亡。这些显著的结果不仅扩展了我们目前对GBP1的理解，而且还具有开发针对炎性小体介导的人类疾病治疗靶点的潜力。
