Outer membrane protein A inhibits the degradation of caspase-1 to regulate NLRP3 inflammasome activation and exacerbate the Acinetobacter baumannii pulmonary inflammation
| Autor: | Zhao Dan, Chunhong Peng, Songjun Shao, Li Yumei, Zijiang Yu, Xiangyan Zhang, Jieru Lin, Bing Guo, Baofei Sun, Yan Yu, Ying Xiao, Mingjun Shi, Laibing Liu, Xiaoyan Yang, Wenjuan Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Acinetobacter baumannii
0301 basic medicine Inflammasomes Interleukin-1beta 030106 microbiology Caspase 1 NLR Proteins Inflammation Microbiology 03 medical and health sciences Ubiquitin NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Gene silencing Receptor integumentary system biology Chemistry Inflammasome Pneumonia respiratory system bacterial infections and mycoses biology.organism_classification 030104 developmental biology Infectious Diseases biology.protein Proteasome inhibitor bacteria medicine.symptom Bacterial Outer Membrane Proteins medicine.drug |
| Zdroj: | Microbial Pathogenesis. 153:104788 |
| ISSN: | 0882-4010 |
| Popis: | Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of caspase-1 degradation by proteasome inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections. |
| Databáze: | OpenAIRE |
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