Macrophages are the versatile sentinels of innate immunity. Originating from embryonic and adult precursors, they populate virtually every tissue, where they orchestrate host defense, homeostasis, and repair. Their phenotypes are not confined to a simple M1/M2 dichotomy; instead, macrophage identity emerges from ontogeny, local niche cues, metabolic state, and epigenetic imprinting. Single-cell and spatial technologies now reveal rich tissue-resident diversity and dynamic state transitions during infection, cancer, autoimmunity, fibrosis, neurodegeneration, cardiometabolic disease and et.al. In parallel, the concepts of immunometabolism and trained innate immunity explain how prior exposures durably re-wire responses—creating opportunities to boost antimicrobial and antitumor functions or to temper pathological inflammation. Yet key challenges remain in harmonizing nomenclature, mapping causality in vivo, and translating macrophage reprogramming into durable, safe therapies.
This Research Topic invites mechanistic, technological, and translational work that clarifies how macrophage identity is specified in tissues, how plasticity is regulated during disease, and how these programs can be rationally manipulated in patients.
• Chart ontogeny, tissue residency, and roles in tissue homeostasis
• Define macrophage contributions to acute and chronic infection, host–pathogen interactions, and vaccine responses
• Dissect tumor-associated macrophages in cancer progression, immune evasion, and therapy response
• Elucidate circuits of inflammation, resolution, fibrosis, and tissue repair/regeneration
• Map crosstalk with microbiota, stromal and endothelial cells, neurons, and adaptive immune cells
• Develop biomarkers/imaging of macrophage states and test therapeutic reprogramming, including combinations with vaccines or immune checkpoint blockade
Article types
• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code
Keywords: macrophage plasticity, tissue-resident macrophages, innate immunity, immunometabolism, epigenetic reprogramming & trained immunity, host–pathogen interactions, inflammation & tissue repair, tumor-associated macrophages (TAMs)
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
