<scp>SIRT1</scp> Attenuates Host Resistance to <i>Salmonella</i> Infection by Negatively Regulating the Immune Responses

Salmonella is a significant zoonotic foodborne pathogen that poses a serious threat to public health and the poultry industry. SIRT1 has been implicated in various biological processes, but its specific role in regulating immune responses during Salmonella infection remains inadequately defined. Our study shows that SIRT1 promotes Salmonella invasion of host cells, and its inhibition impairs intracellular bacterial survival in macrophages. SIRT1 suppresses the secretion of immune factors and attenuates the innate immune response of the host by regulating the NF-κB signaling pathway. Using RNA-Seq, we found that SIRT1 plays a crucial role in host immune responses by modulating pathogen-associated molecular pattern recognition via membrane-bound (TLR-like) and intracellular (NLR-like). Acetylomic analysis revealed that SIRT1 inhibition primarily affects acetylation within metabolic and transcriptional networks. Furthermore, inhibition of SIRT1 activity enhanced the resistance of chicks to Salmonella infection. In summary, our study indicates that SIRT1 promotes Salmonella infection of chicken macrophages and weakens host defense by negatively regulating NF-κB activation and the production of proinflammatory cytokines.