Enhancing immunity against Candida albicans infections through TIGIT knockout

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor on immune cells.
• Candida albicans is a common fungal pathogen causing infections.

Purpose of the Study:

• To investigate the role of TIGIT in host defense against Candida albicans infection.
• To identify the specific fungal ligands for TIGIT.

Main Methods:

• Utilized TIGIT knockout (KO) mice and wild-type (WT) mice.
• Co-cultured TIGIT-KO splenocytes with C. albicans.
• Assessed fungal growth, colonization, survival, and organ burden in a systemic candidiasis model.
• Identified TIGIT-binding fungal proteins using agglutinin-like sequence (ALS) proteins.

Main Results:

• TIGIT-KO mice demonstrated reduced C. albicans fungal growth and colonization.
• TIGIT-KO mice showed improved survival and less body weight loss in a systemic infection model.
• Significantly lower fungal loads were found in kidneys, spleen, and lungs of TIGIT-KO mice.
• Agglutinin-like sequence proteins ALS6, ALS7, and ALS9 of C. albicans were identified as direct ligands for TIGIT.

Conclusions:

• TIGIT plays a significant role in modulating host defense against Candida albicans.
• The interaction between TIGIT and C. albicans ALS proteins is crucial for infection outcome.
• Targeting the TIGIT-C. albicans interaction may offer therapeutic potential for candidiasis.