ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1661395
This article is part of the Research TopicThe Role of Cytosolic Sensors in Host Defense to Intracellular Pathogens and CancerView all articles
Type I interferons regulate nitric oxide production in Brucella abortus-activated microglia contributing to neuronal death
Provisionally accepted
Julia Rodríguez1
Alex David Guano T.1
Ignacio Mazzitelli2
Vida A Dennis3
Ana Maria Rodriguez1
Guillermo Hernán Giambartolomei1,4*- 1Instituto de Inmunología, Genética y Metabolismo (INIGEM), Buenos Aires, Argentina
- 2Instituto de Investigaciones Biomedicas en Retrovirus y SIDA, Buenos Aires, Argentina
- 3Center for NanoBiotechnology Research and Department of Biological Sciences, Alabama State University, Montgomery. AL, United States
- 4National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
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Microglia have a central role in the immunopathogenesis of neurobrucellosis where its activation is a hallmark in this disease. In this study, we present in vitro evidence that type I interferons (IFN) are involved in the activation of microglia during Brucella abortus 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 B. abortus or treated with culture supernatants from B. abortus-infected astocytes. 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-κB 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-κB and STAT1 transcription factors. This observed molecular mechanism contributes to neuronal death induced by B. abortus-activated microglia and may help explain the neurological signs observed in patients with neurobrucellosis.
Keywords: Brucella abortus, Neurobrucellosis, Microglia, Type I Interferons, Nitric Oxide, Neuronal Death
Received: 07 Jul 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Rodríguez, Guano T., Mazzitelli, Dennis, Rodriguez and Giambartolomei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Guillermo Hernán Giambartolomei, National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
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