{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:37:37Z","timestamp":1761709057786},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T00:00:00Z","timestamp":1430956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Enterohaemorrhagic <jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>scherichia coli<\/jats:italic> (<jats:styled-content style=\"fixed-case\">EHEC<\/jats:styled-content>) 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\u2010mediated 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\u20101<jats:italic>\u03b2<\/jats:italic> (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic>) production in human macrophages. Here, we investigated the disparity in Ehx\u2010induced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> production between human and mouse macrophages and explored the underlying mechanism regarding the activation of <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>\u2010like receptor family, pyrin domain containing 3 (<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3) inflammasomes. In contrast to the effects on human differentiated <jats:styled-content style=\"fixed-case\">THP<\/jats:styled-content>\u20101 cells and peripheral blood mononuclear cells, Ehx exerted no effect on <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> production in mouse macrophages and splenocytes because of a disparity in pro\u2010<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> cleavage into mature <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> upon caspase\u20101 activation. Additionally, Ehx significantly contributed to O157:H7\u2010induced <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> release from <jats:styled-content style=\"fixed-case\">THP<\/jats:styled-content>\u20101 cells, which was not detected in mouse macrophages. Confocal microscopy demonstrated that Ehx was a key inducer of cathepsin B release in <jats:styled-content style=\"fixed-case\">THP<\/jats:styled-content>\u20101 cells but not in mouse <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>\u201021 cells upon O157:H7 challenge. Inhibitor experiments indicated that O157:H7\u2010induced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> production was largely dependent upon caspase\u20101 activation and partially dependent upon <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> signalling and cathepsin B release, which were both involved in <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 activation. Moreover, inhibition of K<jats:sup>+<\/jats:sup> efflux drastically diminished O157:H7\u2010induced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> 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.<\/jats:p>","DOI":"10.1111\/imm.12442","type":"journal-article","created":{"date-parts":[[2015,1,10]],"date-time":"2015-01-10T14:38:08Z","timestamp":1420900688000},"page":"258-267","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effect of enterohaemorrhagic <i><scp>E<\/scp>scherichia coli <\/i><scp>O<\/scp>157:<scp>H<\/scp>7\u2010specific enterohaemolysin on interleukin\u20101<i>\u03b2<\/i> production differs between human and mouse macrophages due to the different sensitivity of <scp>NLRP<\/scp>3 activation"],"prefix":"10.1111","volume":"145","author":[{"given":"Yu\u2010Li","family":"Cheng","sequence":"first","affiliation":[{"name":"State Key Laboratory for Infectious Disease Prevention and Control National Institute for Communicable Disease Control and Prevention Chinese Centre for Disease Control and Prevention Beijing China"},{"name":"Department of Medical Microbiology and Parasitology School of Basic Medical Sciences Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010qiong","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Infectious Disease Prevention and Control National Institute for Communicable Disease Control and Prevention Chinese Centre for Disease Control and Prevention Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan\u2010Ming","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Infectious Disease Prevention and Control National Institute for Communicable Disease Control and Prevention Chinese Centre for Disease Control and Prevention Beijing 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