DUSP1 interacts with BIP to regulate Staphylococcus aureus-induced apoptosis through the MAPK signaling pathway.

Staphylococcus aureus (S. aureus) is a major human pathogen that causes apoptosis of immune cells during infection. The rate of apoptosis influences the severity and outcome of the disease, and can be fatal in conditions such as sepsis and septicemia. Dual-specificity phosphatase-1 (DUSP1) is a negative regulator of the mitogen-activated protein kinase (MAPK) signaling pathway in the host innate immune response. However, its role in S. aureus-induced apoptosis remains unexplored. In this study, we investigated the function and underlying regulatory mechanisms of DUSP1 in S. aureus-induced apoptosis. This study revealed that S. aureus infection induces DUSP1 expression and promotes apoptosis. DUSP1 knockdown promotes S. aureus-induced apoptosis, accumulation of reactive oxygen species, and expression of MAPK family member proteins, leading to increased lung tissue injury and poorer intracellular bacterial survival. Furthermore, S. aureus infection elevates the expression of immunoglobulin heavy chain-binding protein (BIP), promotes apoptosis, and enhances the binding of DUSP1 to BIP. Inhibition of BIP enhances S. aureus-induced apoptosis and MAPK signaling pathways. Taken together, these findings demonstrate that S. aureus infection induces DUSP1 and BIP expression, leading to cell apoptosis, and that DUSP1 interacts with BIP to regulate S. aureus-induced apoptosis through the MAPK signaling pathway. Our findings support the regulatory role of DUSP1 in S. aureus-mediated apoptosis, suggesting that DUSP1 is a potential anti-apoptotic therapeutic target.