Innate immune memory after brain injury drives inflammatory cardiac dysfunction

The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored....

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Detalles Bibliográficos
Autores: Simats, Alba, Zhang, Sijia, Messerer, Denise, Chong, Faye, Beşkardeş, Sude, Chivukula, Aparna Sharma, Cao, Jiayu, Besson-Girard, Simon, Montellano, Felipe A., Morbach, Caroline, Carofiglio, Olga, Ricci, Alessio, Roth, Stefan, Llovera, Gemma, Singh, Rashween, Chen, Yiming, Filser, Severin, Plesnila, Nikolaus, Braun, Christian, Spitzer, Hannah, Gokce, Ozgun, Dichgans, Martin, Heuschmann, Peter U., Hatakeyama, Kinta, Beltrán, Eduardo, Clauss, Sebastian, Bonev, Boyan, Schulz, Christian, Liesz, Arthur
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/373268
Acceso en línea:http://hdl.handle.net/10261/373268
https://api.elsevier.com/content/abstract/scopus_id/85199869521
Access Level:acceso abierto
Palabra clave:Brain ischemia
Cardiac fibrosis
Cenicriviroc
Innate immune memory
Interleukin-1
Myeloid cells
Stroke
Systemic inflammation
Trained immunity
Descripción
Sumario:The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1β was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a framework for secondary prevention immunotherapy.

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