{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:49:14Z","timestamp":1778150954705,"version":"3.51.4"},"reference-count":79,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neonatal meningitis\u2010associated\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (NMEC) is among the leading causes of bacterial meningitis and sepsis in newborn infants. Several virulence factors have been identified as common among NMEC, and have been shown to play an important role in the development of bacteremia and\/or meningitis. However, there is significant variability in virulence factor expression between NMEC isolates, and relatively little research has been done to assess the impact of variable virulence factor expression on immune cell activation and the outcome of infection. Here, we investigated the role of NMEC strain\u2010dependent P2X receptor (P2XR) signaling on the outcome of infection in neonatal mice. We found that alpha\u2010hemolysin (HlyA)\u2010expressing NMEC (HlyA\n                    <jats:sup>+<\/jats:sup>\n                    ) induced robust P2XR\u2010dependent macrophage cell death in vitro, while HlyA\n                    <jats:sup>\u2212<\/jats:sup>\n                    NMEC did not. P2XR\u2010dependent cell death was inflammasome independent, suggesting an uncoupling of P2XR and inflammasome activation in the context of NMEC infection. In vivo inhibition of P2XRs was associated with increased mortality in neonatal mice infected with HlyA\n                    <jats:sup>+<\/jats:sup>\n                    NMEC, but had no effect on the survival of neonatal mice infected with HlyA\n                    <jats:sup>\u2212<\/jats:sup>\n                    NMEC. Furthermore, we found that P2XR\u2010dependent protection against HlyA\n                    <jats:sup>+<\/jats:sup>\n                    NMEC in vivo required macrophages, but not neutrophils or NLRP3. Taken together, these data suggest that HlyA\n                    <jats:sup>+<\/jats:sup>\n                    NMEC activates P2XRs which in turn confers macrophage\u2010dependent protection against infection in neonates. In addition, our findings indicate that strain\u2010dependent virulence factor expression should be taken into account when studying the immune response to NMEC.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101485r","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T10:16:33Z","timestamp":1644574593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nucleotide receptors mediate protection against neonatal sepsis and meningitis caused by alpha\u2010hemolysin expressing\n                    <i>Escherichia coli<\/i>\n                    K1"],"prefix":"10.1096","volume":"36","author":[{"given":"Catherine A.","family":"Chambers","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology University of Missouri  Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2337-908X","authenticated-orcid":false,"given":"Jerod A.","family":"Skyberg","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology University of Missouri  Columbia Missouri 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