Extracellular Vesicles Derived from Gram-Negative Bacteria, such asEscherichia coli, Induce Emphysema Mainly via IL-17A–Mediated Neutrophilic Inflammation

Abstract

Recent evidence indicates that Gram-negative bacteria–derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli–derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation. COPD phenotypes and immune responses were evaluated in C57BL/6 wild-type (WT), IFN-γ–deficient, or IL-17A–deficient mice after airway exposure to E. coli EVs. The present study showed that indoor dust from a bed mattress harbors E. coli EVs. Airway exposure to E. coli EVs increased the production of proinflammatory cytokines, such as TNF-α and IL-6. In addition, the repeated inhalation of E. coli EVs for 4 wk induced neutrophilic inflammation and emphysema, which are associated with enhanced elastase activity. Emphysema and elastase activity enhanced by E. coli EVs were reversed by the absence of IFN-γ or IL-17A genes. In addition, during the early period, lung inflammation is dependent on IL-17A and TNF-α, but not on IFN-γ, and also on TLR4. Moreover, the production of IFN-γ is eliminated by the absence of IL-17A, whereas IL-17A production is not abolished by IFN-γ absence. Taken together, the present data suggest that E. coli–derived EVs induce IL-17A–dependent neutrophilic inflammation and thereby emphysema, possibly via upregulation of elastase activity.

Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll‐like receptor 4

“…It is well known that TLR4 signaling is activated by bacterial products, so-called pathogen-associated molecular patterns. Gut microbes are also known to release exosomes containing bacterial toxins that potentially activate macrophage TLR4 signaling (35). However, our PCR sequence demonstrated that there was no 16S rRNA gene amplification to support the presence of bacterial components in preshock or post-T/HS ML exosomes (Fig.…”

IgG Sensitization to Extracellular Vesicles in Indoor Dust Is Closely Associated With the Prevalence of Non-Eosinophilic Asthma, COPD, and Lung Cancer

“… 31 In the future, prospectively designed studies will be needed to evaluate the precise role of cigarette smoking in the development of lung cancer, based on the evidence that bacteria-derived EVs in indoor dust induce neutrophilic pulumonary inflammation and emphysema. 17 21 …”

“… 13 14 Animal experiments have shown that EVs from indoor dust can induce neutrophilic pulmonary inflammation 15 and that airway exposure to bacteria-derived EVs, which are present in indoor dust, can also induce neutrophilic inflammation and subsequently emphysema in the lung. 16 17 Asthma and COPD (with or without emphysema) are characterized by chronic inflammation in the airways. 18 Cancer has also been associated with chronic inflammation.…”

Preparation and Characterization of a Polar Milk Lipid-enriched Component from Whey Powder

“…EVs were isolated from the culture supernatants of E. coli (KCTC 1039) and L. plantarum (KCTC 3108), as described previously (Lee et al, 2009;Kim et al, 2015). Briefly, E. coli and L. plantarum in nutrient broth was cultured at 37℃ and centrifuged twice at 10,000×g for 15 min.…”