Key result
Neutrophil-specific Sting deletion worsens cardiac function and impairs post-reperfusion inflammation resolution after MI.
Why the study?
Prior literature reported contradictory findings on whether neutrophils are detrimental or beneficial in myocardial ischemia/reperfusion injury, and the role of neutrophil-intrinsic STING signaling during MI/R had not been established.
Does neutrophil-specific deletion of Sting impair cardiac function and resolution of inflammation in a preclinical model of myocardial ischemia/reperfusion injury?
Does neutrophil-specific deletion of Sting impair cardiac function and resolution of inflammation in a preclinical model of myocardial ischemia/reperfusion injury?
Neutrophil-intrinsic STING signaling is cardioprotective during myocardial ischemia/reperfusion injury by promoting neutrophil apoptosis, macrophage efferocytosis, and anti-inflammatory macrophage polarization, suggesting that selectively targeting neutrophil effector function is preferable to broad immunosuppression.
Neutrophil-intrinsic STING signaling in MI/R remains hypothesis-generating; leaves open its net effect on injury and any therapeutic targeting.
Neutrophils are the earliest and most abundant immune cells to infiltrate the myocardium after myocardial ischemia/reperfusion (MI/R) injury. To date, the literature presents contradictory findings regarding the detrimental versus beneficial roles of neutrophils in MI/R. Activation of STING (Stimulator of Interferon Genes) signaling drives the expression of proinflammatory cytokines and type I interferons in immune cells. Here, we sought to investigate the role of neutrophil-intrinsic STING signaling during MI/R. Neutrophil-specific deletion of Sting resulted in significantly impaired cardiac function after MI/R, accompanied by reduced activation of NF-κB pathways in cardiac neutrophils, diminished early neutrophil recruitment to the myocardium, and defective neutrophil clearance. Immunostaining demonstrated decreased apoptosis in STING-deficient neutrophils, while flow cytometry showed reduced efferocytosis of these neutrophils by macrophages. Consistent with this, there was a reduction in anti-inflammatory macrophages within the myocardium 72 hours after MI/R. STING signaling in neutrophils is cardioprotective during MI/R by promoting efficient neutrophil clearance and facilitating the resolution of inflammation through the induction of anti-inflammatory macrophage polarization. Collectively, this work supports the concept that selectively targeting neutrophil effector function, rather than employing broad immunosuppression, represents a promising therapeutic strategy for MI/R.
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Brockman et al. (2026) studied Myocardial ischemia/reperfusion injury. Neutrophil-specific deletion of Sting vs. Intact neutrophil STING signaling was evaluated on Cardiac function and inflammation resolution after myocardial ischemia/reperfusion. Neutrophil-specific Sting deletion impaired cardiac function, neutrophil clearance, and anti-inflammatory macrophage polarization 72 hours after myocardial ischemia/reperfusion.
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