Enhancing immunity against infections through TIGIT knockout.

Unlabelled: T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is an inhibitory receptor expressed by T and natural killer cells. Here, we used TIGIT knockout (KO) mice to demonstrate that mouse TIGIT directly interacts with . Reduced fungal growth and colonization were observed when TIGIT-KO splenocytes were co-cultured with compared to the wild type (WT). In a systemic candidiasis model, TIGIT-KO mice exhibited improved survival and reduced body weight loss compared to WT mice. Organ-specific fungal burden assessment revealed significantly lower fungal loads in the kidneys, spleen, and lungs of TIGIT-KO mice. Finally, we show that the agglutinin-like sequence proteins ALS6, ALS7, and ALS9 of are ligands for TIGIT and that the absence of these proteins abolishes the TIGIT effect . Our results identify the significance of TIGIT in modulating host defense against and highlight the potential therapeutic implications for infections.

Importance: Our results identify the significance of T cell immunoreceptor with immunoglobulin and ITIM domain in modulating host defense against and highlight the potential therapeutic implications for infections.