{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:14:45Z","timestamp":1778685285032,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"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":["Immunol. Cell Biol."],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neonatal meningitis\u2010associated <jats:italic>Escherichia coli<\/jats:italic> (NMEC) is a leading cause of sepsis and meningitis in newborn infants. Neonates are known to have impaired inflammasome activation and interleukin (IL)\u20101 production. However, it is unknown what role this plays in the context of NMEC infection. Here we investigated the role of IL\u20101 signaling in the pathogenesis of NMEC infection. We found both IL\u20101\u03b2 and IL\u20101\u03b1 were secreted from macrophages and microglial cells in response to NMEC in a Toll\u2010like receptor 4\u2010 and NLR family pyrin domain containing 3 (NPLR3)\u2010dependent manner. Intracerebral infection of adult mice indicated a protective role of IL\u20101 signaling during NMEC infection. However, IL\u20101 receptor blockade in wild\u2010type neonatal mice did not significantly alter bacterial loads in the blood or brain, and we, therefore, investigated whether protection conferred by IL\u20101 was age dependent. Neonates are known to have increased nitric oxide (NO) levels compared with adults, and we found NO inhibited the secretion of IL\u20101 by macrophages in response to NMEC. In contrast to our results in wild\u2010type neonates, blockade of IL\u20101 receptor in neonates lacking inducible nitric oxide synthase (iNOS) led to significantly increased bacterial loads in the blood and brain. These data indicate IL\u20101 signaling is protective during NMEC infection in neonates only when iNOS is absent. Collectively, our findings suggest that increased NO production by neonates inhibits IL\u20101 production, and that this suppresses the protective role of IL\u20101 signaling in response to NMEC infection. This may indicate a general mechanism for increased susceptibility of neonates to infection and could lead to new therapeutic strategies in the future.<\/jats:p>","DOI":"10.1111\/imcb.12445","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T13:06:40Z","timestamp":1612703200000},"page":"596-610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nitric oxide inhibits interleukin\u20101\u2010mediated protection against <i>Escherichia coli<\/i> K1\u2010induced sepsis and meningitis in a neonatal murine model"],"prefix":"10.1111","volume":"99","author":[{"given":"Catherine A","family":"Chambers","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn A","family":"Lacey","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology University of Missouri Columbia MO USA"},{"name":"Department of Immunology Duke University Medical Center Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana C","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerod A","family":"Skyberg","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology University of Missouri Columbia MO 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