{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:45:59Z","timestamp":1785735959824,"version":"3.56.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"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. Mol. Neurosci."],"abstract":"<jats:p>Traumatic brain injury (TBI) induces a dynamic immune response that increases susceptibility to infectious complications, particularly ventilator-associated pneumonia, bloodstream infections, and central nervous system infections. These infections prolong mechanical ventilation and intensive care unit stay and may adversely affect neurological recovery. This vulnerability is driven by brain injury-induced immune suppression, characterized by a coexisting inflammatory response and a compensatory immunodepression, including lymphopenia, impaired antigen presentation, monocyte and neutrophil dysfunction, reduced cytokine responsiveness, and neuroendocrine dysregulation. Bidirectional neuro-immune interactions contribute to these alterations: damage-associated molecular patterns and microglial activation initiate neuroinflammation, while sympathetic hyperactivation and hypothalamic-pituitary-adrenal axis dysfunction promote peripheral immune impairment. Emerging pathways, including cGAS-STING signaling, may further link neuronal injury, neuroinflammation, and immune paralysis. This narrative review examines experimental and clinical evidence for targeted immunomodulatory strategies intended to reduce infectious complications after TBI while avoiding exacerbation of secondary brain injury. Candidate approaches include granulocyte-macrophage and granulocyte colony-stimulating factors, interferon-\u03b3 and interleukin-7, mesenchymal stromal cells, and neuromodulatory interventions targeting adrenergic or cholinergic pathways. Although several strategies have restored immune cell function or reduced infectious burden in preclinical models, clinical translation remains limited by small heterogeneous cohorts, variable timing of intervention, and insufficient assessment of infection-centered outcomes. A central challenge is that post-TBI immunity is dynamic and heterogeneous, ranging from hyperinflammatory to profoundly immunosuppressed profiles, while likely differing between the central nervous system and the peripheral\/systemic immune compartments. Biomarker-guided identification of immune endotypes may therefore be essential to select appropriate interventions and therapeutic windows. Sex-related immune differences may also influence infection risk and treatment response through the immunomodulatory and barrier-protective effects of sex hormones. Future studies should combine serial immune profiling with clinically meaningful infectious and neurological outcomes. Precision immunomodulation, tailored to immune phenotype, timing, and potentially sex-hormone status, may provide a rational strategy to reduce infectious morbidity and improve outcomes after TBI.<\/jats:p>","DOI":"10.3389\/fnmol.2026.1902464","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:30:12Z","timestamp":1785735012000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuro\u2013immune dysregulation after traumatic brain injury: immunomodulatory strategies to prevent infectious complications"],"prefix":"10.3389","volume":"19","author":[{"given":"Sylvain","family":"Gourier","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Brest University Hospital Centre","place":["Brest, France"]},{"name":"Univ Brest, Laboratoire ORPHY EA 4324","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Botquelen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Brest University Hospital Centre","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Langeron","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Brest University Hospital Centre","place":["Brest, France"]},{"name":"Univ Brest, Laboratoire ORPHY EA 4324","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Caillard","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Brest University Hospital Centre","place":["Brest, France"]},{"name":"Univ Brest, Laboratoire ORPHY EA 4324","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Bouras","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Brest University Hospital Centre","place":["Brest, France"]},{"name":"Univ Brest, INSERM, EFS, UMR 1078, GGB","place":["Brest, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s12974-018-1354-7","article-title":"STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury.","volume":"15","author":"Abdullah","year":"2018","journal-title":"J. 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