Cyclic GMP-AMP synthase (cGAS) is an important cytosolic DNA sensor that plays a crucial role in triggering STING-dependent signal and inducing type I interferons (IFNs). cGAS is important for intracellular bacterial recognition and innate immune responses. However, the regulating effect of the cGAS pathway for bone marrow-derived dendritic cells (BMDCs) during Mycobacterium bovis (M. bovis) infection is still unknown. We hypothesized that the maturation and activation of BMDCs were modulated by the cGAS/STING/TBK1/IRF3 signaling pathway. In this study, we found that M. bovis promoted phenotypic maturation and functional activation of BMDCs via the cGAS signaling pathway, with the type I IFN and its receptor (IFNAR) contributing. Additionally, we showed that the type I IFN pathway promoted CD4⁺ T cells’ proliferation with BMDC during M. bovis infection. Meanwhile, the related cytokines increased the expression involved in this signaling pathway. These data highlight the mechanism of the cGAS and type I IFN pathway in regulating the maturation and activation of BMDCs, emphasizing the important role of this signaling pathway and BMDCs against M. bovis. This study provides new insight into the interaction between cGAS and dendritic cells (DCs), which could be considered in the development of new drugs and vaccines against tuberculosis.

Mycobacterium bovis is the causative agent of bovine tuberculosis, has been identified a serious threat to human population. It has been found that sodium butyrate (NaB), the inhibitor of histone deacetylase, can promote the expression of cathelicidin (LL37) and help the body to resist a variety of injuries. In the current study, we investigate the therapeutic effect of NaB on the regulation of host defense mechanism against M. bovis infection. We found an increased expression of LL37 in M. bovis infected THP-1 cells after NaB treatment. In contrast, NaB treatment significantly down-regulated the expression of Class I HDAC in THP-1 cells infected with M. bovis. Additionally, NaB reduced the expression of phosphorylated P65 (p-P65) and p-IκBα, indicating the inhibition of nuclear factor-κB (NF-κB) signaling. Furthermore, we found that NaB treatment reduced the production of inflammatory cytokines (IL-1β, TNF-α, and IL-10) and a key anti-apoptotic marker protein Bcl-2 in THP-1 cell infected with M. bovis. Notably, mice showed high resistance to M. bovis infection after NaB treatment. The reduction of viable M. bovis bacilli indicates that NaB-induced inhibition of M. bovis infection mediated by upregulation of LL37 and inhibition of NF-κB signaling pathway. These observations illustrate that NaB mediate protective immune responses against M. bovis infection. Overall, these results suggest that NaB can be exploited as a therapeutic strategy for the control of M. bovis in animals and human beings.

The problem of veterinary drug residues in black-feathered silky fowl (BFS) has garnered significant attention. This study investigated the residue elimination patterns and causes of enrofloxacin (ENR), sulfachloropyrazine sodium (SPZ), and doxycycline (DOX) in BFS using ultra-high performance liquid chromatography mass spectrometry (UPLC-MS), along with the drug adsorption and melanin binding tests. The findings indicated that ENR and SPZ were metabolized slowly, DOX was metabolized faster in BFS, with optimum withdrawal time was 87.8, 37.26, and 24.7 days, respectively. The adsorption capacity of skin + fat to drugs and the binding capacity of melanin to the three drugs in BFS were in the order of ENR > SPZ > DOX, confirming that melanin's binding ability influences the drug residues in BFS. This study is highly significant for addressing the issue of veterinary drug residues in BFS.

Mycobacterium tuberculosis (Mtb) infection can trigger immune responses in macrophages during its autophagy and apoptosis, as two crucial cellular processes which are essential for the host to clear the pathogen. Resveratrol (RES) is a natural polyphenolic compound with various biological functions such as anti-inflammatory, antioxidant, and immunomodulatory activities. However, the specific mechanism by which it regulates autophagy and apoptosis in a Bacillus Calmette-Guérin (BCG)-infected macrophage model remains to be elucidated. This study aimed to analyze the effects of RSE on BCG-induced autophagy and apoptosis in macrophages and explore the underlying molecular mechanisms. The mouse macrophage cell line RAW264.7 was used to establish a BCG infection model and evaluate the interventional effects of RES. Cell viability was detected by CCK-8 assay. The expression levels of autophagy- and apoptosis-related proteins were analyzed by Western blotting. LC3 puncta formation was observed by immunofluorescence. Autophagy rate and apoptosis rate were determined by flow cytometry. The ultrastructure of autophagosomes and autolysosomes was observed by transmission electron microscopy. The results showed that BCG infection significantly increased the expression of LC3-II, Beclin1, Atg5, and Atg7 in macrophages; decreased p62 levels; and increased the number of intracellular autophagosomes and autolysosomes. Concurrently, BCG infection also induced apoptosis, including upregulation of Bax, Caspase 3, Caspase 9, and PARP1 expression; downregulation of Bcl-2 expression; and an increased apoptosis rate. RES promoted autophagosome accumulation and inhibited apoptosis in BCG-infected macrophages in a concentration-dependent manner; however, these effects were significantly attenuated after SIRT1 gene silencing by siRNA and inhibition by EX527. Therefore, it is speculated that RES may regulate autophagy and apoptosis through the SIRT1/FOXO1 pathway. These findings provide a potential experimental basis for developing RES into a host-directed therapeutic (HDT) agent, and offer new insights into the mechanisms by which natural products participate in host defense.