AUTHOR=Paulovičová Ema , Paulovičová Lucia , Hrubiško Martin , Krylov Vadim B. , Argunov Dmitry A. , Nifantiev Nikolay E. 

TITLE=Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01273

DOI=10.3389/fimmu.2017.01273

ISSN=1664-3224

ABSTRACT=The study is oriented at the in vitro evaluation of the immunobiological activity and efficacy of synthetically prepared isomeric pentasaccharides representing fragments of Aspergillus fumigatus cell-wall galactomannan and containing β-(1→5)-linked tetragalactofuranoside chain attached to O-6 (GM-1) or O-3 (GM-2) of a spacer-armed mannopyranoside residue. These compounds were studied as biotinylated conjugates which both demonstrated immunomodulatory activities on the RAW 264.7 cell line murine macrophages as in vitro innate immunity cell-model. Immunobiological studies revealed time- and concentration-dependent efficient immunomodulation. The proliferation of RAW 264.7 macrophages was induced at higher concentration (100 μg/mL) of studied glycoconjugates and longer exposure (48 h), with more pronounced efficacy for GM-1. The increase of proliferation followed the previous increase of IL-2 production. The cytokine profile of the macrophages treated with the glycoconjugates was predominantly pro-inflammatory Th1 type with significant increase of TNFα, IL-6 and IL-12 release for both glycoconjugates. The RAW 264.7 macrophages production of free radicals was not significantly affected by glycoconjugates stimulation. The phagocytic activity of RAW 264.7 cells was reduced following GM-1 treatment and was significantly increased after 24h stimulation with GM-2, contrary to 48 h stimulation. Moreover, the synthetically prepared galactomannoside derivatives have been evaluated as efficient serodiagnostic antigens recognized by specific Ig-isotypes, and significant presence of specific IgM antibodies in serum of patients suffering from vulvovaginitis was observed.