Cholesteryl 6-O-acyl-α-glucosides from diverse Helicobacter spp. signal through the C-type lectin receptor Mincle

Area of Science:

• Microbiology
• Immunology
• Organic Chemistry

Background:

• Helicobacter species are Gram-negative bacteria implicated in various diseases.
• These bacteria produce cholesteryl α-glucosides, potential pathogen-associated molecular patterns.
• Understanding these molecules is key to deciphering host-pathogen interactions.

Purpose of the Study:

• To synthesize and characterize Helicobacter spp. cholesteryl 6-O-acyl-α-glucosides (αCAGs).
• To investigate the immunomodulatory activity of αCAGs and cholesteryl α-glucoside (αCG) via the Mincle receptor.
• To establish a molecular basis for the immunobiology of non-pylori Helicobacter infections.

Main Methods:

• Stereoselective α-glucosylation of cholesterol using a trifluoroacetimidate donor.
• Synthesis of αCG and various αCAGs with different acyl chain lengths (C12:0 to C18:1).
• Stimulation assays using human and mouse Mincle receptors to assess immune activation.

Main Results:

• Synthesis of αCG and a series of αCAGs was achieved.
• All synthesized αCAGs potently activated both human and mouse Mincle receptors.
• αCG showed weak activation of human Mincle and no activation of mouse Mincle.

Conclusions:

• Helicobacter spp. αCAGs are potent Mincle agonists, explaining their role in immune activation.
• The acyl chain composition of αCAGs does not significantly affect Mincle agonism.
• These findings provide critical insights into the immune response against non-pylori Helicobacter infections.