| First Author | Cheng YL | Year | 2015 |
| Journal | Immunology | Volume | 145 |
| Issue | 2 | Pages | 258-67 |
| PubMed ID | 25580516 | Mgi Jnum | J:247035 |
| Mgi Id | MGI:5923741 | Doi | 10.1111/imm.12442 |
| Citation | Cheng YL, et al. (2015) Effect of enterohaemorrhagic Escherichia coli O157:H7-specific enterohaemolysin on interleukin-1beta production differs between human and mouse macrophages due to the different sensitivity of NLRP3 activation. Immunology 145(2):258-67 |
| abstractText | Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection in humans can cause acute haemorrhagic colitis and severe haemolytic uraemic syndrome. The role of enterohaemolysin (Ehx) in the pathogenesis of O157:H7-mediated disease in humans remains undefined. Recent studies have revealed the importance of the inflammatory response in O157:H7 pathogenesis in humans. We previously reported that Ehx markedly induced interleukin-1beta (IL-1beta) production in human macrophages. Here, we investigated the disparity in Ehx-induced IL-1beta production between human and mouse macrophages and explored the underlying mechanism regarding the activation of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasomes. In contrast to the effects on human differentiated THP-1 cells and peripheral blood mononuclear cells, Ehx exerted no effect on IL-1beta production in mouse macrophages and splenocytes because of a disparity in pro-IL-1beta cleavage into mature IL-1beta upon caspase-1 activation. Additionally, Ehx significantly contributed to O157:H7-induced ATP release from THP-1 cells, which was not detected in mouse macrophages. Confocal microscopy demonstrated that Ehx was a key inducer of cathepsin B release in THP-1 cells but not in mouse IC-21 cells upon O157:H7 challenge. Inhibitor experiments indicated that O157:H7-induced IL-1beta production was largely dependent upon caspase-1 activation and partially dependent upon ATP signalling and cathepsin B release, which were both involved in NLRP3 activation. Moreover, inhibition of K(+) efflux drastically diminished O157:H7-induced IL-1beta production and cytotoxicity. The findings in this study may shed light on whether and how the Ehx contributes to the development of haemolytic uraemic syndrome in human O157:H7 infection. |
