Pathogen-derived oligosaccharides improve innate immune response to intracellular parasite infection.

Pathogen glycolipids, including Leishmania spp. lipophosphoglycan (LPG) and Mycobacterium tuberculosis mannosylated lipoarabinomannan (ManLAM), modulate essential interactions with host phagocytic cells. Polysaccharide and lipid components promote immunomodulation.

Synthesis of multivalent tuberculosis and Leishmania-associated capping carbohydrates reveals structure-dependent responses allowing immune evasion.

Mycobacterium tuberculosis and the protozoan parasites of the genus Leishmania are intracellular pathogens that can survive in macrophages--the very white blood cells of the immune system responsible for engulfing and ultimately clearing foreign invaders. The ability of these pathogens to hide within immune cells has made the design of effective therapies, including vaccines, to control tuberculosis and leishmaniasis particularly challenging. Herein we present the synthesis and development of carbohydrate-based probes to demonstrate that changes in pathogen-associated surface oligosaccharides are sufficient to alter cellular immune responses and thereby let a pathogen hide from immune surveillance.