Outer membrane protein A of Acinetobacter baumannii regulates pulmonary inflammation through the TLR2-NF-κB pathway
Copyright © 2023 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:284 |
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| Enthalten in: |
Veterinary microbiology - 284(2023) vom: 20. Sept., Seite 109812 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yumei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 04.09.2023 Date Revised 04.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.vetmic.2023.109812 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acinetobacter baumannii | |
| 650 | 4 | |a Inflammasome | |
| 650 | 4 | |a Outer membrane protein A (ompA) | |
| 650 | 4 | |a Pneumonia | |
| 650 | 4 | |a TLR2-NF-κB pathway | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a Toll-Like Receptor 2 |2 NLM | |
| 650 | 7 | |a OMPA outer membrane proteins |2 NLM | |
| 650 | 7 | |a 149024-69-1 |2 NLM | |
| 650 | 7 | |a Caspase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.36 |2 NLM | |
| 700 | 1 | |a Liu, Laibing |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Chaolun |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Baofei |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Shipeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiangyan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Zijiang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaoying |e verfasserin |4 aut | |
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