Innate immune memory after brain injury drives inflammatory cardiac dysfunction

Area of Science:

• Immunology
• Neurology
• Cardiology

Background:

• Stroke's long-term impact includes chronic comorbidities.
• Systemic immune responses post-stroke are not well understood.
• Myeloid innate immune memory is a potential cause of remote organ dysfunction.

Purpose of the Study:

• To investigate the role of systemic immunity in post-stroke comorbidities.
• To identify immunological mechanisms driving remote organ dysfunction after stroke.
• To explore targeted immunotherapies for secondary stroke prevention.

Main Methods:

• Single-cell sequencing to analyze immune cell changes.
• In vivo mouse models of stroke and cardiac dysfunction.
• Analysis of cardiac tissue from mice and human stroke patients.
• Interleukin-1 beta (IL-1β) neutralization and CCR2/5 inhibition.

Main Results:

• Persistent pro-inflammatory changes in monocytes/macrophages observed up to 3 months post-stroke.
• Cardiac fibrosis and dysfunction were identified in mice and human patients.
• IL-1β drives epigenetic changes in innate immune memory, inducing cardiac dysfunction.
• Blocking IL-1β or CCR2/5 prevented post-stroke cardiac dysfunction.

Conclusions:

• Myeloid innate immune memory contributes to remote organ dysfunction after stroke.
• IL-1β is a key mediator of stroke-induced cardiac complications.
• Targeting IL-1β and monocyte trafficking offers a therapeutic strategy for secondary stroke prevention.