{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:52:01Z","timestamp":1792900321454,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Influenza A virus (IAV) infection is primarily associated with respiratory disease; however, accumulating evidence indicates that neurotropic strains can induce central nervous system (CNS) inflammation and contribute to persistent neurological dysfunction. Aberrant immune activation is thought to play a critical role in these outcomes, yet therapeutic approaches that effectively attenuate neuroinflammation while preserving antiviral immunity remain limited. Immunometabolic regulators, including the endogenous metabolite itaconate, have recently emerged as key modulators of innate immune responses, although their contribution to virus-induced CNS pathology remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the present study, we investigated whether systemic administration of itaconate or its structural isomer mesaconate modulates neuroinflammatory responses and hippocampal synaptic integrity during infection with the neurotropic IAV strain rSC35M (mouse-adapted A\/Seal\/Mass\/ 1\/80, H7N7). Using a murine model, treatment was initiated at the onset of clinical symptoms, and both peripheral and central immune responses were assessed at the peak of disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>Neither itaconate nor mesaconate significantly altered overall disease severity, as assessed by body weight loss, although mesaconate attenuated infection-associated hypothermia. Pulmonary inflammatory responses were largely unaffected by treatment; in contrast, mesaconate selectively reduced IL-1\u03b2 levels in the brain. At the cellular level, H7N7 infection induced pronounced microglial activation within hippocampal subregions, characterized by increased cell density and soma volume, altered process complexity, and enhanced engulfment of postsynaptic material. These infection-induced microglial alterations were partially prevented by mesaconate treatment and largely abrogated by itaconate treatment. Notably, attenuation of microglial density and reactivity during the acute phase was associated with long-term preservation of hippocampal synaptic plasticity. Collectively, these findings indicate that therapeutic administration of itaconate and mesaconate, potentially through distinct mechanisms, can modulate microglia-driven synaptic pathology during neurotropic IAV infection. Targeting immunometabolic pathways may therefore represent a promising strategy to prevent persistent neurological sequelae associated with viral disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1776302","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:49:27Z","timestamp":1772520567000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting neuroinflammation: itaconate and mesaconate as therapeutic strategies against H7N7 influenza-associated CNS damage"],"prefix":"10.3389","volume":"17","author":[{"given":"Melanie","family":"Ohm","sequence":"first","affiliation":[{"name":"Department of Cellular Neurobiology, Zoological Institute, Technische Universit\u00e4t (TU) Braunschweig","place":["Braunschweig, 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