Innate immune lectins kill bacteria expressing blood group antigen

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• ABO(H) blood group antigen expression on self-cells eliminates self-reactive antibody-producing cells, limiting adaptive immunity against pathogens with similar antigens.
• This immune tolerance creates a vulnerability to infections by microbes expressing cognate blood group antigens.

Purpose of the Study:

• To investigate potential innate immune defense mechanisms against pathogens expressing blood group antigens.
• To identify innate proteins capable of recognizing and neutralizing such pathogens.

Main Methods:

• Screening of innate immune proteins for recognition of human blood group antigens.
• In vitro and in vivo assays to assess the activity of identified lectins against specific bacterial strains.
• Analysis of the killing mechanism, including domain mediation, complement independence, and membrane integrity disruption.

Main Results:

• Two intestinal innate immune lectins, galectin-4 (Gal-4) and Gal-8, were identified.
• Gal-4 and Gal-8 specifically recognize and kill human blood group antigen-expressing Escherichia coli.
• Killing activity is rapid, complement-independent, mediated by C-terminal domains, and involves membrane integrity disruption.
• These lectins did not affect other bacterial strains, indicating specificity.

Conclusions:

• Innate defense lectins, such as Gal-4 and Gal-8, can confer immunity against pathogens displaying blood group-like antigens.
• This provides a crucial defense mechanism in the absence of robust adaptive immunity.
• Highlights the role of innate immunity in host defense against specific microbial threats.