{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:29:36Z","timestamp":1786706976433,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Neutrophils are key effectors of innate immunity. Although traditionally regarded as short-lived effector cells, recent evidence suggests they can undergo functional reprogramming after microbial stimulation, leading to trained immunity. We investigated whether lipopolysaccharide (LPS) or Candida albicans \u03b2-glucan induces memory-like inflammatory responses in adult peripheral and neonatal cord blood neutrophils. We used complementary molecular and functional approaches to characterize neutrophil responses following in vitro priming with LPS or \u03b2-glucan and subsequent LPS restimulation. Cytokine secretion, reactive oxygen species (ROS) production, glycolytic activity (via lactate production and glycolytic enzyme expression), and ERK1\/2 and NF-\u03baB signaling pathway activation were assessed. Priming with LPS or \u03b2-glucan enhanced neutrophil responsiveness to secondary stimulation, resulting in increased secretion of IL-1\u03b2, IL-6, IL-8, CXCL1, and CCL2, together with elevated ROS production. These effects were consistently more pronounced in neonatal than in adult neutrophils. Memory-like neutrophils also exhibited metabolic reprogramming, associated by increased hexokinase-2 and phosphofructokinase-1 mRNA expression, elevated lactate production, and enhanced ERK1\/2 and NF-\u03baB activation. Human neutrophils, particularly neonatal cells, develop memory-like characteristics following LPS or \u03b2-glucan priming, highlighting their functional and metabolic plasticity and suggesting a role for neutrophil training in early-life immune adaptation.<\/jats:p>","DOI":"10.3390\/ijms27167268","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"7268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LPS and \u03b2-Glucan Induce Differential Memory-like Inflammatory Responses with Enhanced Reactivity in Neonatal Neutrophils Compared to Adults"],"prefix":"10.3390","volume":"27","author":[{"given":"Lisa","family":"Zagler","sequence":"first","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Snaidr","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3718-5507","authenticated-orcid":false,"given":"Natascha","family":"K\u00f6stlin-Gille","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Hildenbrand","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Kliegel","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"Department of Anaesthesiology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Surgery and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricarda","family":"Will","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6326-6281","authenticated-orcid":false,"given":"Stefanie","family":"Dietz-Ziegler","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cahit","family":"Birdir","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gille","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-589X","authenticated-orcid":false,"given":"Trim","family":"Lajqi","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Medical Faculty Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41573-019-0054-z","article-title":"Neutrophils as Emerging Therapeutic Targets","volume":"19","author":"Sperandio","year":"2020","journal-title":"Nat. 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