title: Extracellular vesicles derived from Gram-negative bacteria, such as Escherichia 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.
authors.affiliation: Asan Institute for Life Science, Seoul 138-736, Republic of Korea; Ulsan University College of Medicine, Seoul 138-736, Republic of Korea;
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea;
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea;
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Choi
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine, Seoul 158-710, Republic of Korea; and.
authors.forename: Jun-Pyo
authors.initials: JP
authors.lastname: Choi
authors.affiliation: Asan Institute for Life Science, Seoul 138-736, Republic of Korea;
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Heo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea;
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.affiliation: Department of Internal Medicine, Dankook University College of Medicine, Cheonan 330-714, Republic of Korea.
authors.forename: Young-Koo
authors.initials: YK
authors.lastname: Jee
authors.affiliation: Asan Institute for Life Science, Seoul 138-736, Republic of Korea; Ulsan University College of Medicine, Seoul 138-736, Republic of Korea; juinea@ewha.ac.kr ymoh55@amc.seoul.kr.
authors.forename: Yeon-Mok
authors.initials: YM
authors.lastname: Oh
authors.affiliation: Institute of Convergence Medicine, Ewha Womans University School of Medicine, Seoul 158-710, Republic of Korea; and juinea@ewha.ac.kr ymoh55@amc.seoul.kr.
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
mesh_terms: D016902:Air Pollution, Indoor; D000818:Animals; D055252:Cell-Derived Microparticles / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004391:Dust; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism*; D005110:Extracellular Space; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011656:Pulmonary Emphysema / Q000378:metabolism* / Q000382:microbiology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D004391:Dust; D020381:Interleukin-17; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D007371:Interferon-gamma