Bacterial Outer Membrane Vesicle-Mediated Cytosolic Delivery of Flagellin Triggers Host NLRC4 Canonical Inflammasome Signaling

Yang, Jungmin; Hwang, Inhwa; Lee, Eun‐Ju; Shin, Sung Jae; Lee, Eun Jin; Rhee, Joon Haeng; Yu, Je-Wook

doi:10.3389/fimmu.2020.581165

Cited by 46 publications

(43 citation statements)

References 35 publications

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“…This is because bacterial EVs are loaded with various immune-stimulating ligands (e.g., LPS, peptidoglycan, lipoprotein, and bacterial nucleic acids) which can be identified by pathogen recognition receptors and activate the host immune system ( Kaparakis-Liaskos and Ferrero, 2015 ). Yang et al (2020) found that flagellated bacteria, Pseudomonas aeruginosa ( P. aeruginosa ) and Salmonella , secreted EVs that stimulated the NLRC4 inflammasome pathways via flagellin-mediated transfer to the host cytoplasm. Moraxella catarrhalis ( M. catarrhalis ) EVs induce B cell activation via the TLR2 and TLR9 pathways ( Vidakovics et al, 2010 ).…”

Section: The Functions Of Bacterial Extracellular Vesiclesmentioning

confidence: 99%

Inhibitors of Bacterial Extracellular Vesicles

et al. 2022

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Both Gram-positive and Gram-negative bacteria can secrete extracellular vesicles (EVs), which contain numerous active substances. EVs mediate bacterial interactions with their hosts or other microbes. Bacterial EVs play a double-edged role in infections through various mechanisms, including the delivery of virulence factors, modulating immune responses, mediating antibiotic resistance, and inhibiting competitive microbes. The spread of antibiotic resistance continues to represent a difficult clinical challenge. Therefore, the investigation of novel therapeutics is a valuable research endeavor for targeting antibiotic-resistant bacterial infections. As a pathogenic substance of bacteria, bacterial EVs have gained increased attention. Thus, EV inhibitors are expected to function as novel antimicrobial agents. The inhibition of EV production, EV activity, and EV-stimulated inflammation are considered potential pathways. This review primarily introduces compounds that effectively inhibit bacterial EVs and evaluates the prospects of their application.

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Section: The Functions Of Bacterial Extracellular Vesiclesmentioning

confidence: 99%

Inhibitors of Bacterial Extracellular Vesicles

et al. 2022

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“…OMVs are highly effective in modulating innate immune responses in the host without direct host cell-bacterial interactions since they contain many immune-reactive proteins originating from their parent bacterium [69]. In terms of structure and biological activity, bacteria-derived OMVs are similar to mammalian cell-derived EVs (exosomes).…”

Section: Immunomodulatory Host-bacteria Communicationsmentioning

confidence: 99%

“…H. pyroli OMVs have been found within infected gastric mucosa of H. pyroliinfected patients who suffered from gastric disease [72]. Salmonella typhimurium (S. typhimurium) OMVs promote flagellin-mediated caspase-1 activation and IL-1β secretion in an endocytosis-dependent manner [69]. OMVs from H. pyroli, Neisseria, Pseudomonas, Campylobacter, and Vibrio cause non-phagocytic epithelial cells to secrete interleukin-8 (IL-8), a chemokine generated by a number of tissues and blood cells [73,74].…”

Section: Immunomodulatory Host-bacteria Communicationsmentioning

confidence: 99%

Biomimetic Nanoparticles Coated with Bacterial Outer Membrane Vesicles as a New-Generation Platform for Biomedical Applications

et al. 2021

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The biomedical field is currently reaping the benefits of research on biomimetic nanoparticles (NPs), which are synthetic nanoparticles fabricated with natural cellular materials for nature-inspired biomedical applications. These camouflage NPs are capable of retaining not only the physiochemical properties of synthetic nanoparticles but also the original biological functions of the cellular materials. Accordingly, NPs coated with cell-derived membrane components have achieved remarkable growth as prospective biomedical materials. Particularly, bacterial outer membrane vesicle (OMV), which is a cell membrane coating material for NPs, is regarded as an important molecule that can be employed in several biomedical applications, including immune response activation, cancer therapeutics, and treatment for bacterial infections with photothermal activity. The currently available cell membrane-coated NPs are summarized in this review. Furthermore, the general features of bacterial OMVs and several multifunctional NPs that could serve as inner core materials in the coating strategy are presented, and several methods that can be used to prepare OMV-coated NPs (OMV-NPs) and their characterization are highlighted. Finally, some perspectives of OMV-NPs in various biomedical applications for future potential breakthrough are discussed. This in-depth review, which includes potential challenges, will encourage researchers to fabricate innovative and improvised, new-generation biomimetic materials through future biomedical applications.

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“…Type IV bacterial pilus can activate noncanonical inflammasome signaling. In addition, bacterial-released outer membrane vesicles have been shown to activate the inflammasome through delivered LPS and flagellin [12,13]. Furthermore, LL-37, an epithelial antimicrobial immunomodulatory peptide, can act on other epithelial cells to promote the NLRP3 inflammasome in response to P. aeruginosa infection [14].…”

Section: Introductionmentioning

confidence: 99%

The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection

et al. 2022

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The innate immune response to P. aeruginosa pulmonary infections relies on a network of pattern recognition receptors, including intracellular inflammasome complexes, which can recognize both pathogen- and host-derived signals and subsequently promote downstream inflammatory signaling. Current evidence suggests that the inflammasome does not contribute to bacterial clearance and, in fact, that dysregulated inflammasome activation is harmful in acute and chronic P. aeruginosa lung infection. Given the role of mitochondrial damage signals in recruiting inflammasome signaling, we investigated whether mitochondrial-targeted therapies could attenuate inflammasome signaling in response to P. aeruginosa and decrease pathogenicity of infection. In particular, we investigated the small molecule, ZLN005, which transcriptionally activates peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, antioxidant defense, and cellular respiration. We demonstrate that P. aeruginosa infection promotes the expression of inflammasome components and attenuates several components of mitochondrial repair pathways in vitro in lung epithelial cells and in vivo in an acute pneumonia model. ZLN005 activates PGC-1α and its downstream effector, Sirtuin 3 (SIRT3), a mitochondrial-localized deacetylase important for cellular metabolic processes and for reactive oxygen species homeostasis. ZLN005 also attenuates inflammasome signaling induced by P. aeruginosa in bronchial epithelial cells and this action is dependent on ZLN005 activation of SIRT3. ZLN005 treatment reduces epithelial-barrier dysfunction caused by P. aeruginosa and decreases pathogenicity in an in vivo pneumonia model. Therapies that activate the PGC-1α—SIRT3 axis may provide a complementary approach in the treatment of P. aeruginosa infection.

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Bacterial Outer Membrane Vesicle-Mediated Cytosolic Delivery of Flagellin Triggers Host NLRC4 Canonical Inflammasome Signaling

Cited by 46 publications

References 35 publications

Inhibitors of Bacterial Extracellular Vesicles

Inhibitors of Bacterial Extracellular Vesicles

Biomimetic Nanoparticles Coated with Bacterial Outer Membrane Vesicles as a New-Generation Platform for Biomedical Applications

The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection

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