Trained immunity in skin infections: Macrophages and beyond

The skin is frequently subjected to minor mechanical insults that may compromise its barrier integrity and permit the entry of pathogens. Therefore, the immune system of the skin needs to rapidly balance antimicrobial defense with tissue repair. To maintain homeostasis, the skin relies both on acute immune defenses and on mechanisms of innate memory or trained immunity. This enhanced inflammatory response to a second challenge has been well characterized in bone marrow cells, such as monocytes, monocyte-derived macrophages, and stem cells. Yet, the specific memory responses in skin-resident immune cells remain less understood. Importantly, the common skin colonizer Staphylococcus aureus has been identified as a potent inducer of trained immunity, triggering both metabolic and epigenetic changes at local sites such as the skin, and centrally in the bone marrow. This review explores the emerging understanding of trained immunity in the skin, that is how infection-driven cellular processes induce long-lasting immune adaptation and modulate skin barrier integrity.