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Acid‐Triggered Degradable Reagents for Differentiation of Adaptive and Innate Immune Responses to Leishmania ‐Associated Sugars
Author(s) -
Roychoudhury Rajarshi,
Martinez Pedro A.,
GrinnagePulley Tara,
Schaut Robert G.,
Petersen Christine A.,
Pohl Nicola L. B.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201502807
Subject(s) - chemistry , immune system , innate immune system , leishmania , antigen presentation , linker , macrophage , microbiology and biotechnology , cell growth , cell , t cell , biochemistry , receptor , biology , immunology , computer science , operating system , parasite hosting , world wide web , in vitro
Abstract Lipopolysaccharides (LPS) of Leishmania spp are known to alter innate immune responses. However, the ability of these sugars to specifically alter adaptive T‐cell responses is unclear. To study cap sugar–T‐cell interactions, pathogen mimics (namely glycodendrimer‐coated latex beads with acid‐labile linkers) were synthesized. Upon lysosomal acidification, linker breakdown releases glycodendrimers for possible loading on antigen presenting molecules to induce T‐cell growth. T‐cell proliferation was indeed higher after macrophage exposure to mannobioside or ‐trioside‐containing glycodendrimers than to non‐functionalized beads. Yet, blocking phagolysosomal acidification only reduced T‐cell proliferation with macrophages exposed to beads with an acid‐labile‐linker and not to covalently‐linked beads. These sugar‐modified reagents show that oligosaccharides alone can drive T‐cell proliferation by acidification‐requiring presentation, most significantly in NKT receptor (CD160)‐restricted T cells.