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

ABSTRACT: 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.

SUBMITTER: Song EH

PROVIDER: S-EPMC3816587 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Song Eun-Ho EH Osanya Alex O AO Petersen Christine A CA Pohl Nicola L B NL

Journal of the American Chemical Society 20100801 33

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 ca ...[more]

PMID: 20669964

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Leishmania major degrades murine CXCL1 - An immune evasion strategy.

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Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection.

Project description:Leishmaniasis, a neglected tropical disease, currently infects approximately 12 million people worldwide with 1 to 2 million new cases each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more efficient synthesis was designed, with a tethered fluorophore. Further attachment of the glycodendrimer to a biocompatible, surface eroding microparticle allows for targeted uptake and internalization of the pathogen-associated oligosaccharide by phagocytic immune cells. The α-1,2-trimannose-linked bioerodible microparticles were found to be safe after administration into the footpad of mice and demonstrated a similar response to α-1,2-trimannose-coated latex beads during L. major footpad infection. Furthermore, the bioerodible microparticles allowed for investigation of the role of pathogen-associated oligosaccharides for recognition by pathogen-recognition receptors during L. major-induced leishmaniasis.

| S-EPMC6423605 | biostudies-literature

Carbohydrates as potentially versatile core subcarriers for multivalent immunogens.

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Glycosphingolipid synthesis mediates immune evasion in Kras-driven cancer

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2024-06-30 | GSE270660 | GEO

Glycosphingolipid synthesis mediates immune evasion in Kras-driven cancer

2024-06-26 | PXD052718 | Pride

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