Trained Immunity as a Preventive Measure for Surgical Site Infections

Even with strict implementation of preventive measures, surgical site infections (SSIs) remain among the most prevalent health care-associated infections. New strategies to prevent SSIs would thus have a huge impact, also in light of increasing global rates of antimicrobial drug resistance. Considering the indispensable role of innate immune cells in host defense in surgical wounds, enhancing their function may represent a potential strategy for prevention of SSIs. Trained immunity is characterized by metabolic, epigenetic, and functional reprogramming of innate immune cells. These functional changes take place at multiple levels, namely, at the level of bone marrow precursors, circulating innate immune cells, and resident tissue macrophages. Experimental studies have shown that induction of trained immunity can protect against various infections. Increasing evidence suggests that it may also lower the risk and severity of SSIs. This may occur through several different mechanisms. First, trained immunity enhances local host defense against soft tissue infections, including those caused by Staphylococcus aureus, the most common cause of SSIs. Second, training effects on nonimmune cells such as fibroblasts have been shown to improve wound repair. Third, trained immunity may prevent or reverse the postoperative immunoparalysis that contributes to risk of infections following surgery. There are multiple approaches to inducing trained immunity, such as vaccination with the bacillus Calmette-Guérin (BCG) tuberculosis vaccine, topical administration of β-glucan, or treatment with the Toll-like receptor 7 agonist imiquimod. Clinical-experimental studies should establish if and how induction of trained immunity can best help prevent SSIs and what patient groups would most benefit.