Precision immunotherapy for sepsis: Harnessing passive IgE to Activate M2 macrophages

Sepsis is a rapidly progressing and often fatal medical emergency caused by uncontrolled immune activation in response to infection. The ensuing cytokine storm drives systemic inflammation, leading to multiple organ dysfunction and high mortality rates worldwide. Recent advances highlight the critical role of M2 macrophages, which counteract excessive inflammation, facilitate tissue repair, and help reestablish immune homeostasis. This review explores a novel immunotherapeutic strategy: the use of passive immunoglobulin E/allergen complexes (IgE-ACs) to selectively engage CD23 receptors on M2 macrophages. By promoting anti-inflammatory cytokine release and limiting tissue injury, this targeted approach has the potential to restore immune balance and improve clinical outcomes in sepsis. The current evidence, mechanisms of action, and a prophetic example is discussed to illustrate the promise and challenges of this emerging therapy.