Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb). Apoptosis and necrosis caused by the interaction between the host and the pathogen, as well as the host’s inflammatory response, play an important role in the pathogenesis of TB. Dual-specificity phosphatase 1 (DUSP1) plays a vital role in regulating the host immune responses. However, the role of DUSP1 in the regulation of THP-1 macrophage apoptosis induced by attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection remains unclear. In the present study, we report that infection with BCG significantly induces macrophage apoptosis and induces the production of DUSP1, TNF-α and IL-1β. DUSP1 knockdown significantly inhibited BCG-induced macrophage apoptosis and activation of MAPKs/NF-κB signaling pathway. In addition, DUSP1 knockdown suppressed BCG-induced inflammation in vivo. Taken together, this study demonstrates that DUSP1, as a regulator of MAPKs/NF-κB signaling pathway, plays a novel role in BCG-induced macrophage apoptosis and inflammatory response.

Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb). Apoptosis and necrosis caused by the interaction between the host and the pathogen, as well as the host’s inflammatory response, play an important role in the pathogenesis of TB. Dual-specificity phosphatase 1 (DUSP1) plays a vital role in regulating the host immune responses. However, the role of DUSP1 in the regulation of THP-1 macrophage apoptosis induced by attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection remains unclear. In the present study, we report that infection with BCG significantly induces macrophage apoptosis and induces the production of DUSP1, TNF-α and IL-1β. DUSP1 knockdown significantly inhibited BCG-induced macrophage apoptosis and activation of MAPKs/NF-κB signaling pathway. In addition, DUSP1 knockdown suppressed BCG-induced inflammation in vivo. Taken together, this study demonstrates that DUSP1, as a regulator of MAPKs/NF-κB signaling pathway, plays a novel role in BCG-induced macrophage apoptosis and inflammatory response.

Staphylococcus aureus (S. aureus) is a major human pathogen that causes apoptosis of immune cells during infections. The rate of apoptosis influences the severity and outcome of the disease, which can be fatal for infections including sepsis and septicemia. Dual specificity phosphatase-1 (DUSP1) is a negative regulator of MAPK signaling pathways in the host innate immune response, but its role in S. aureus-induced apoptosis remains unexplored. We used western blotting and immunofluorescence assays to show that S. aureus infection induced DUSP1 expression and promoted apoptosis in THP-1 cells. Knockdown of DUSP1 using an siRNA construct promoted the expression of key pro-apoptotic proteins, including cleaved-caspase3, cleaved-PARP1, cleaved-caspase9, cytochrome c and bax, whereas it inhibited the expression of key apoptosis inhibitory proteins bcl-2 and bcl-XL. These results were validated by flow cytometry. In addition, knockdown of DUSP1 promoted the accumulation of reactive oxygen species in S. aureus-induced macrophages, and mechanistically, knockdown of DUSP1 promoted the phosphorylation of target molecules in the MAPK signaling pathway, thereby promoting apoptosis in S. aureus-infected THP-1 macrophages. These data support a regulatory role for DUSP1 in S. aureus-mediated apoptosis and we suggest that DUSP1 be investigated as an anti-apoptotic therapeutic target.

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