{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:56:39Z","timestamp":1778824599610,"version":"3.51.4"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Microglia have a central role in the immunopathogenesis of neurobrucellosis where its activation is a hallmark in this disease. In this study, we present <jats:italic>in vitro<\/jats:italic> evidence that type I interferons (IFN) are involved in the activation of microglia during <jats:italic>Brucella abortus<\/jats:italic> infection and are necessary to induce neuronal death. Neutralization of type I IFN receptor (IFNAR) on microglia cells completely abrogates neuronal loss in primary co-cultures of neurons\/microglia infected with <jats:italic>B. abortus<\/jats:italic> or treated with culture supernatants from <jats:italic>B. abortus<\/jats:italic>-infected astrocytes. Type I IFN regulate inducible nitric oxide synthase (iNOS) expression, and subsequently nitric oxide (NO) production in microglia by increasing STAT1 expression and phosphorylation. Our results also show that NF-\u03baB and the MAPK signaling pathways, ERK1\/2 and p38, are implicated in the secretion of type I IFN induced by the bacterium. Finally, our results indicate that iNOS induction and NO production require activation of both NF-\u03baB and STAT1 transcription factors. This observed molecular mechanism contributes to neuronal death induced by <jats:italic>B. abortus<\/jats:italic>-activated microglia and may help explain the neurological signs observed in patients with neurobrucellosis.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1661395","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:14:28Z","timestamp":1756268068000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Type I interferons regulate nitric oxide production in Brucella abortus-activated microglia contributing to neuronal death"],"prefix":"10.3389","volume":"16","author":[{"given":"Julia","family":"Rodr\u00edguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex 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