Phagocytic aberrations in macrophages in asthma: a mechanistic systematic review integrating in vitro, animal, and human evidence

Objective To integrate evidence from human, animal, and in vitro studies to elucidate the molecular mechanisms underlying phagocytic aberrations in asthmatic macrophages and to construct a cross-hierarchical mechanistic framework. Methods This systematic review followed the PRISMA 2020 statement. PubMed and Web of Science Core Collection were searched from inception to March 6, 2026. We included original human, animal, and cellular studies on asthma that investigated macrophage phagocytic function and reported related molecular mechanisms. Two independent reviewers performed screening, data extraction, and quality assessment. Due to substantial heterogeneity across studies, a narrative synthesis approach was used to integrate the evidence. Results A total of 37 studies, published between 1982 and 2025, were ultimately included. Overall, macrophage phagocytic function in asthma is characterized by aberrations dependent on clinical phenotype, phagocytic substrate, and the microenvironment. Based on the included studies, the relevant mechanisms were categorized into eight categories: dysregulation of phagocytic receptor signaling; defects at various stages of efferocytosis; immunometabolic reprogramming; aberrant signal transduction; regulation by immunomodulatory factors; acquired alterations in cellular function; circadian clock regulation; and other unclassified mechanisms. Conclusion Phagocytic aberrations in macrophages in asthma represent a complex process driven by a multi-layered, interconnected molecular network. These aberrations contribute to the persistence of chronic airway inflammation, increased susceptibility to infection, elevated risk of acute exacerbations, and the development of severe or refractory asthma. Systematic integration of these mechanisms enhances the understanding of innate immune dysfunction in asthma and provides a theoretical basis for developing therapeutic strategies targeting macrophage phagocytic function. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261332569.