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Int J Med Microbiol. 2018 Oct;308(7):882-889. doi: 10.1016/j.ijmm.2018.06.004. Epub 2018 Jun 19.

Enterohemorrhagic Escherichia coli O157 outer membrane vesicles induce interleukin 8 production in human intestinal epithelial cells by signaling via Toll-like receptors TLR4 and TLR5 and activation of the nuclear factor NF-κB.

Author information

1
Institute for Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, Münster, 48149, Germany; National Institute of Public Health, National Reference Laboratory for E. coli and Shigella, Prague, 100 42, Czech Republic. Electronic address: martina.bielaszewska@szu.cz.
2
National Institute of Public Health, National Reference Laboratory for E. coli and Shigella, Prague, 100 42, Czech Republic.
3
Institute for Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, Münster, 48149, Germany.
4
Institute for Hygiene and the National Consulting Laboratory for Hemolytic Uremic Syndrome, University of Münster, Münster, 48149, Germany; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, 48149, Germany.

Abstract

Proinflammatory cytokines play important roles in the pathogenesis of diseases caused by enterohemorrhagic Escherichia coli (EHEC) O157, but the spectrum of bacterial components involved in the proinflammatory responses is not fully understood. Here, we investigated the abilities of outer membrane vesicles (OMVs), nanoparticles released by EHEC O157 during growth, to induce production of proinflammatory cytokines in human intestinal epithelial cells. OMVs from both EHEC O157:H7 and sorbitol-fermenting (SF) EHEC O157:H- induced production of interleukin-8 (IL-8) in Caco-2, HCT-8, and HT-29 intestinal epithelial cell lines. H7 flagellin was the key IL-8-inducing component of EHEC O157:H7 OMVs, whereas cytolethal distending toxin V and O157 lipopolysaccharide (LPS) largely contributed to IL-8 production elicited by flagellin-lacking OMVs from SF EHEC O157:H-. The H7 flagellin-mediated signaling via Toll-like receptor (TLR) 5, and O157 LPS-mediated signaling via TLR4/MD-2 complex, which were followed by activation of the nuclear factor NF-κB were major pathways underlying IL-8 production induced by EHEC O157 OMVs. The proinflammatory and immunomodulatory capacities of EHEC O157 OMVs have pathogenetic implications and support the OMVs as suitable vaccine candidates.

KEYWORDS:

Enterohemorrhagic Escherichia coli O157; Flagellin; Immunomodulation; Lipopolysaccharide; Outer membrane vesicles; Proinflammatory cytokines

PMID:
29934223
DOI:
10.1016/j.ijmm.2018.06.004
[Indexed for MEDLINE]

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