AUTHOR=Lee Jaewook , Yoon Yae Jin , Kim Ji Hyun , Dinh Nhung Thi Hong , Go Gyeongyun , Tae Sookil , Park Kyong-Su , Park Hyun Taek , Lee Changjin , Roh Tae-Young , Di Vizio Dolores , Gho Yong Song 

TITLE=Outer Membrane Vesicles Derived From Escherichia coli Regulate Neutrophil Migration by Induction of Endothelial IL-8

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02268

DOI=10.3389/fmicb.2018.02268

ISSN=1664-302X

ABSTRACT=Outer membrane vesicles (OMVs) are spherical, proteolipid nanostructures that are constitutively released by Gram-negative bacteria including Escherichia coli. While it has been shown that administration of E. coli OMVs stimulates a strong pulmonary inflammatory response with infiltration of neutrophils into the lungs in vivo, the mechanism of E. coli OMV-mediated neutrophil recruitment is poorly characterized. In this study, we observed significant infiltration of neutrophils into the mouse lung tissues in vivo, with increased expression of the neutrophil chemoattractant CXCL1, a murine functional homologue of human IL-8, upon intraperitoneal administration of E. coli OMVs. In addition, OMVs and CD31-positive endothelial cells co-localized in the mouse lungs. Moreover, in vitro results showed that E. coli OMVs significantly increased IL-8 release from human microvascular endothelial cells and Toll-like receptor (TLR)4 was found to be the main component for recognizing E. coli OMVs among human endothelial cell-associated TLRs. Furthermore, the transmigration of neutrophils was suppressed in the lung tissues obtained from TLR4 knock-out mice treated with E. coli OMVs. Taken together, our data demonstrated that E. coli OMVs potently recruit neutrophils into the lung via the release of IL-8/CXCL1 from endothelial cells in TLR4- and NF-κB-dependent manners.