Spermidine Associated with Gut Microbiota Protects Against MRSA Bloodstream Infection by Promoting Macrophage M2 Polarization

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen that causes various diseases. Extensive researches highlight the significant role of gut microbiota and its metabolites, particularly spermidine, in infectious diseases. However, the immunomodulatory mechanisms of spermidine in MRSA-induced bloodstream infection remain unclear. Here, we confirmed the protective effects of spermidine in bloodstream infection in mice. Spermidine reduced the bacterial load and expression of inflammatory factors by shifting the macrophage phenotype to an anti-inflammatory phenotype, ultimately prolonging the survival of the infected mice. The protective effect against MRSA infection may rely on the elevated expression of protein tyrosine phosphatase nonreceptor 2 (PTPN2). Collectively, these findings confirm the immunoprotective effects of spermidine via binding to PTPN2 in MRSA bloodstream infection, providing new ideas for the treatment of related infectious diseases.