Project description:Siglec-9 has been of particular interest for their potential as immune checkpoints. Here, we employed docking-based virtual screening combined with bio-layer interferometry assays to identify a potential Siglec-9 inhibitor, MTX-3937. Analysis showed that MTX-3937-treatment significantly enhanced the production of IFN-γ, TNF-α, perforin and CD107a in human NK cells. Consistently, MTX-3937 largely promoted NK cells tumor killing activities both in vitro and in vivo. In mechanism, MTX-3937 inhibited the phosphorylation level of SHP-1/2 in NK92 cells.
Project description:Investigation of whole genome gene expression level changes in the phytopathogenic Dickeya dadantii wild-type strain 3937 during an acute per os infection of an aphid body, in comparison with a colony grown in standard LB medium. The pathosystem described in this study has been analysed and first published in Grenier et al. 2006, and further detailed in Costechareyre et al. 2011
Project description:Background Dickeya dadantii is a necrotrophic pathogen causing disease in many plants. Previous studies have demonstrated that the type III secretion system (T3SS) of D. dadantii is required for full virulence. HrpL is an alternative sigma factor that binds to the hrp box promoter sequence of T3SS genes to up-regulate their expression. Methodology/Principal Findings To explore the inventory of HrpL-regulated genes of D. dadantii 3937 (3937), transcriptome profiles of wild-type 3937 and a hrpL mutant grown in a T3SS-inducing medium were examined. Using a cut-off value of 1.5, significant differential expression was observed in sixty-three genes, which are involved in various cellular functions such as type III secretion, chemotaxis, metabolism, regulation, and stress response. A hidden Markov model (HMM) was used to predict candidate hrp box binding sites in the intergenic regions of 3937, including the promoter regions of HrpL-regulated genes identified in the microarray assay. In contrast to biotrophic phytopathgens such as Pseudomonas syringae, among the HrpL up-regulated genes in 3937 only those within the T3SS were found to contain a hrp box sequence. Moreover, direct binding of purified HrpL protein to the hrp box was demonstrated for hrp box-containing DNA fragments of hrpA and hrpN using the electrophoretic mobility shift assay (EMSA). In this study, a putative T3SS effector DspA/E was also identified as a HrpL-upregulated gene, and shown to be translocated into plant cells in a T3SS-dependent manner. Conclusion/Significances We provide the genome-wide study of HrpL-regulated genes in a necrotrophic phytopathogen (D. dadantii 3937) through a combination of transcriptomics and bioinformatics, which led to identification of several effectors. Our study indicates the extent of differences for T3SS effector protein inventory requirements between necrotrophic and biotrophic pathogens, and may allow the development of different strategies for disease control for these different groups of pathogens.