Bacterial Outer Membrane Vesicles and Immune Modulation of the Host

Charpentier, Lily A.; Dolben, Emily F.; Hendricks, Matthew R.; Hogan, Deborah A.; Bomberger, Jennifer M.; Stanton, Bruce A.

doi:10.3390/membranes13090752

Cited by 9 publications

(4 citation statements)

References 120 publications

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“…CF-HBECs from three donors were exposed to either vehicle, the same number of V-OMVs, or 40% more Tobi-OMVs, to represent the increased secretion of OMVs induced by tobramycin in the in vitro experiments. The concentration of OMVs used was in the range of bacterial vesicles measured in biological fluids, including BALF, in vivo [reviewed in (28, 29)]. After a six-hour exposure, the basolateral medium was collected and cytokines were interogated by 41-plex ELISA.…”

Section: Resultsmentioning

confidence: 99%

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P. aeruginosatRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis

Li,

Barnaby,

Nymon

et al. 2024

Preprint

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Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density ofPseudomonas aeruginosa (P. aeruginosa)in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5′ tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates ofP. aeruginosa. The 5′ tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion. In mouse lung, increased expression of the 5′ tRNA-fMet halves in OMVs attenuated KC secretion and neutrophil recruitment. Furthermore, there was less IL-8 and neutrophils in bronchoalveolar lavage fluid isolated from pwCF during the period of exposure to tobramycin versus the period off tobramycin. In conclusion, we have shown in mice andin vitrostudies on CF-HBEC that tobramycin reduces inflammation by increasing 5′ tRNA-fMet halves in OMVs that are delivered to CF-HBEC and reduce IL-8 and neutrophilic airway inflammation. This effect is predicted to improve lung function in pwCF receiving tobramycin forP. aeruginosainfection.New and noteworthyThe experiments in this report identify a novel mechanim whereby tobramycin reduces inflammation in two models of CF. Tobramycin increased the secretion of tRNA-fMet haves in OMVs secreted byP. aeruginiosa, which reduced the OMV-LPS induced inflammatory response in primary cultures of CF-HBEC and in mouse lung, an effect predicted to reduce lung damage in pwCF.Graphical abstractThe anti-inflammatory effect of tobramycin mediated by 5′ tRNA-fMet halves secreted inP. aeruginosaOMVs.(A)P. aeruginosacolonizes the CF lungs and secrets OMVs. OMVs diffuse through the mucus layer overlying bronchial epithelial cells and induce IL-8 secretion, which recruits neutrophils that causes lung damage. (B) Tobramycin increases 5′ tRNA-fMet halves in OMVs secreted byP. aeruginosa. 5′ tRNA-fMet halves are delivered into host cells after OMVs fuse with lipid rafts in CF-HBEC and down-regulate protein expression of MAPK10, IKBKG, and EP300, which suppresses IL-8 secretion and neutrophils in the lungs. A reduction in neutrophils in CF BALF is predicted to improve lung function and decrease lung damage.

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Section: Resultsmentioning

confidence: 99%

“…OMVs were added to the apical side in a total of 500ul ALI medium. Previous studies have shown that the concentration of OMVs in biological fluids including BALF are ∼10 10 /ml (reviewed in (28, 29)). After a six-hour exposure, the basolateral media was collected for cytokine measurements.…”

Section: Methodsmentioning

confidence: 99%

P. aeruginosatRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis

Li,

Barnaby,

Nymon

et al. 2024

Preprint

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“…In contrast, phage amplification in situ within bacterial biofilms, which is part of the advantages of this therapeutic alternative compared to traditional antibiotics, would probably be morphologically different, and thus, likely recognized by the respiratory epithelium using additional receptors. Phages are released from their bacterial hosts following replication along with outer membrane vesicles, which modify airway epithelial responses [ 61 , 62 ]. How mammalian cells respond to different phages following secondary rounds of replication is unknown.…”

Section: Discussionmentioning

confidence: 99%

Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells

Zamora,

Reidy,

Armbruster

et al. 2024

PLoS Biol

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Phage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells (AECs) derived from a person with cystic fibrosis (CF), we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.

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“…These EVs contain cytoplasm, membrane molecules, and mycobacterial cell wall lipoproteins. References: Brown et al [ 28 ] (structure of bacterial membranes); Schwechheimer and Kuehn [ 29 ] and Charpentier et al [ 30 ] (vesiculation in Gram-negative bacteria); Briaud and Carrol [ 31 ] (vesiculation in Gram-positive bacteria); Gupta et al [ 32 ]; and Palacios et al [ 14 ] (vesiculation in M. tuberculosis ). Created with .…”

Section: Figurementioning

confidence: 99%

The Role of Bacterial Extracellular Vesicles in the Immune Response to Pathogens, and Therapeutic Opportunities

Peregrino,

Castañeda-Casimiro,

Vázquez-Flores

et al. 2024

IJMS

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Pathogenic bacteria have several mechanisms to evade the host’s immune response and achieve an efficient infection. Bacterial extracellular vesicles (EVs) are a relevant cellular communication mechanism, since they can interact with other bacterial cells and with host cells. In this review, we focus on the EVs produced by some World Health Organization (WHO) priority Gram-negative and Gram-positive pathogenic bacteria; by spore-producing bacteria; by Mycobacterium tuberculosis (a bacteria with a complex cell wall); and by Treponema pallidum (a bacteria without lipopolysaccharide). We describe the classification and the general properties of bacterial EVs, their role during bacterial infections and their effects on the host immune response. Bacterial EVs contain pathogen-associated molecular patterns that activate innate immune receptors, which leads to cytokine production and inflammation, but they also contain antigens that induce the activation of B and T cell responses. Understanding the many effects of bacterial EVs on the host’s immune response can yield new insights on the pathogenesis of clinically important infections, but it can also lead to the development of EV-based diagnostic and therapeutic strategies. In addition, since EVs are efficient activators of both the innate and the adaptive immune responses, they constitute a promising platform for vaccine development.

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Bacterial Outer Membrane Vesicles and Immune Modulation of the Host

Cited by 9 publications

References 120 publications

P. aeruginosatRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis

P. aeruginosatRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis

Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells

The Role of Bacterial Extracellular Vesicles in the Immune Response to Pathogens, and Therapeutic Opportunities

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