The clinical role of host and bacterial-derived extracellular vesicles in pneumonia

Jung, Anna Lena; Schmeck, Bernd; Wiegand, Marie; Bedenbender, Katrin; Benedikter, Birke J.

doi:10.1016/j.addr.2021.05.021

Cited by 14 publications

(17 citation statements)

References 153 publications

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“…Considering the different developmental origin and priming of these macrophages, it is conceivable that AMs would have shown a weaker pro-inflammatory response in contrast to BDMs. Bacterial vesicles are already used in vaccination strategies against different pneumonia-inducing pathogens (reviewed in [ 42 ]). Hence, OMVs do not only represent a tool for potential systemic vaccination strategies against their host bacteria, but could also be used locally to combat viral infections by activating resident innate immune cells.…”

Section: Discussionmentioning

confidence: 99%

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis

et al. 2023

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Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As important resident immune cells, alveolar macrophages are located at the air-tissue interface where they comprise the first line of defence against inhaled microorganisms and particles. To date, little is known about the interplay between alveolar macrophages and OMVs from pathogenic bacteria. The immune response to OMVs and underlying mechanisms are still elusive. Here, we investigated the response of primary human macrophages to bacterial vesicles (Legionella pneumophila, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Streptococcus pneumoniae) and observed comparable NF-κB activation across all tested vesicles. In contrast, we describe differential type I IFN signalling with prolonged STAT1 phosphorylation and strong Mx1 induction, blocking influenza A virus replication only for Klebsiella, E.coli and Salmonella OMVs. OMV-induced antiviral effects were less pronounced for endotoxin-free Clear coli OMVs and Polymyxin-treated OMVs. LPS stimulation could not mimic this antiviral status, while TRIF knockout abrogated it. Importantly, supernatant from OMV-treated macrophages induced an antiviral response in alveolar epithelial cells (AEC), suggesting OMV-induced intercellular communication. Finally, results were validated in an ex vivo infection model with primary human lung tissue. In conclusion, Klebsiella, E.coli and Salmonella OMVs induce antiviral immunity in macrophages via TLR4-TRIF-signaling to reduce viral replication in macrophages, AECs and lung tissue. These gram-negative bacteria induce antiviral immunity in the lung through OMVs, with a potential decisive and tremendous impact on bacterial and viral coinfection outcome.

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Section: Discussionmentioning

confidence: 99%

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis

et al. 2023

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“…Generation of EVs by host cells can occur via outward budding of the plasma membrane, resulting in microvesicles. Alternatively, inward budding of the endosomal membrane results in multivesicular endosomes (MVEs) with intraluminal vesicles (Jung et al, 2021). They contain a variety of molecular components such as nucleic acids (DNA, RNA), proteins, lipids, and other organic substances.…”

Section: Figurementioning

confidence: 99%

Extracellular vesicles derived from host and gut microbiota as promising nanocarriers for targeted therapy in osteoporosis and osteoarthritis

Cheung

Ma²,

Xingxuan³

et al. 2023

Front. Pharmacol.

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Osteoporosis (OP), a systemic bone disease that causes structural bone loss and bone mass loss, is often associated with fragility fractures. Extracellular vesicles (EVs) generated by mammalian and gut bacteria have recently been identified as important mediators in the intercellular signaling pathway that may play a crucial role in microbiota-host communication. EVs are tiny membrane-bound vesicles, which range in size from 20 to 400 nm. They carry a variety of biologically active substances across intra- and intercellular space. These EVs have developed as a promising research area for the treatment of OP because of their nanosized architecture, enhanced biocompatibility, reduced toxicity, drug loading capacity, ease of customization, and industrialization. This review describes the latest development of EVs derived from mammals and bacteria, including their internalization, isolation, biogenesis, classifications, topologies, and compositions. Additionally, breakthroughs in chemical sciences and the distinctive biological features of bacterial extracellular vesicles (BEVs) allow for the customization of modified BEVs for the therapy of OP. In conclusion, we give a thorough and in-depth summary of the main difficulties and potential future of EVs in the treatment of OP, as well as highlight innovative uses and choices for the treatment of osteoarthritis (OA).

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“…To sum up, there is growing evidence that, as part of the secretome, the extracellular vesicles (EVs) will be the next effective therapeutic agents deriving from MSCs. Current research concerning MSC-EVs [125,126] as anti-inflammatory [127] and pro-regenerative agents for treating inflammation-related conditions has shown therapeutic potential in preclinical studies as recently reviewed [128]. In most of the cases persistent infections led to increased tissue damage associated with excessive duration of inflammation.…”

Section: Mscs As Source Of Antibiotic-free Nanomaterialsmentioning

confidence: 99%

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

Marrazzo

Pizzuti

Zia³

et al. 2021

Antibiotics

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Antibiotic resistance is creating enormous attention on the development of new antibiotic-free therapy strategies for bacterial diseases. Mesenchymal stromal stem cells (MSCs) are the most promising candidates in current clinical trials and included in several cell-therapy protocols. Together with the well-known immunomodulatory and regenerative potential of the MSC secretome, these cells have shown direct and indirect anti-bacterial effects. However, the low reproducibility and standardization of MSCs from different sources are the current limitations prior to the purification of cell-free secreted antimicrobial peptides and exosomes. In order to improve MSC characterization, novel label-free functional tests, evaluating the biophysical properties of the cells, will be advantageous for their cell profiling, population sorting, and quality control. We discuss the potential of emerging microfluidic technologies providing new insights into density, shape, and size of live cells, starting from heterogeneous or 3D cultured samples. The prospective application of these technologies to studying MSC populations may contribute to developing new biopharmaceutical strategies with a view to naturally overcoming bacterial defense mechanisms.

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The clinical role of host and bacterial-derived extracellular vesicles in pneumonia

Cited by 14 publications

References 153 publications

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis

Bacterial vesicles block viral replication in macrophages via TLR4-TRIF-axis

Extracellular vesicles derived from host and gut microbiota as promising nanocarriers for targeted therapy in osteoporosis and osteoarthritis

Microfluidic Tools for Enhanced Characterization of Therapeutic Stem Cells and Prediction of Their Potential Antimicrobial Secretome

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