TIGIT limits anti-bacterial immunity and is a potential target for immunotherapy

Abstract Inhibitory receptors called “immune checkpoints” restrict overzealous immune responses during inflammatory events such as infection or cancer. Blocking the function of these checkpoints using monoclonal antibodies can tip balance towards activation and disease clearance, which has been a revelation in treatment various cancers. Considering recent advances have shown that dysregulation evasion are shared hallmarks cancer persistent bacterial infection, better understanding may uncover novel therapeutic targets to help direct host clearing pathogens. In this study, we use murine model SalmonellaTyphimurium investigate how regulate immunity infection. We found lymphocytes from infected mice exhibit phenotype suggestive dysfunction, characterised by upregulation multiple co-inhibitory checkpoints. Most strikingly, T cell immunoglobulin ITIM domain (TIGIT) was upregulated on majority CD4 +T cells. used RNA-sequencing ex vivostimulation cells show ligation TIGIT leads significant functional deficiencies, including reductions proliferation pro-inflammatory cytokine production. Importantly, blockade checkpoint vivousing anti-TIGIT able enhance leading improved clearance. Taken together, research suggests targeting potential restore bacteria managing serious F.S.F.G is funded UQ Frazer Institute Laboratory Start-Up Package, T.R.M. supported HDR PhD Scholarship.