炎症体
鲍曼不动杆菌
TLR2型
微生物学
促炎细胞因子
生物
信号转导衔接蛋白
基因沉默
NF-κB
炎症
信号转导
细胞生物学
免疫学
细菌
基因
生物化学
TLR4型
遗传学
铜绿假单胞菌
作者
Yumei Li,Laibing Liu,Chaolun Xiao,Baofei Sun,Sanzhong Luo,Dawei Yang,Xiangyan Zhang,Tao Huang,Yu Zhou,Xiaoying Li
标识
DOI:10.1016/j.vetmic.2023.109812
摘要
Acinetobacter baumannii (A. baumannii) is characterized by a high prevalence of drug resistance; how to effectively treat it is still a major clinical challenge. Our previous experiments confirmed that ompA, which is one of the most well-characterized virulence factors, may be dependent on the caspase-1 pathway-stimulated expression of NLRP3 inflammasome to enhance inflammation. TLRs (i.e., TLR2, etc.) is the initiating signal for NLRP3 inflammasome activation; how it relates to ompA in its underlying pathogenic mechanism is not clear. In this study, we proofed that ompA promoted NLRP3 inflammasome activation while the TLR2-NF-κB pathway was also activated after A. baumannii infection. Additionally, the expression of NLRP3 inflammasome-associated proteins and genes was inhibited by silencing TLR2 and NLRP3. This indicated that ompA might depend on the TLR2-NF-κB pathway to assemble and activate the NLRP3 inflammasome. OmpA promoted the assembly of the NLRP3 inflammasome through the TLR2-NF-κB pathway and inhibited the degradation of caspase-1 by the proteasome so that a large number of mature IL-1β/IL-18 and other proinflammatory factors were released extracellularly to enhance the body’s inflammatory response. Taken together, the results of the joint pre-study confirmed a novel TLR2-NF-κB/NLRP3/caspase-1-modulated mechanism underpinning ompA activity, the NLRP3 inflammasome pathway may be as a potential immunomodulatory target against A. baumannii infections.
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