Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan

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)...

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Main Authors: Ema Paulovičová, Lucia Paulovičová, Martin Hrubiško, Vadim B. Krylov, Dmitry A. Argunov, Nikolay E. Nifantiev
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.01273/full
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author Ema Paulovičová
Lucia Paulovičová
Martin Hrubiško
Vadim B. Krylov
Dmitry A. Argunov
Nikolay E. Nifantiev
author_facet Ema Paulovičová
Lucia Paulovičová
Martin Hrubiško
Vadim B. Krylov
Dmitry A. Argunov
Nikolay E. Nifantiev
author_sort Ema Paulovičová
collection DOAJ
description 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 24 h 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.
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spelling doaj.art-cc4394a14e844f028cd1ab0987f872f12022-12-22T00:55:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01273287999Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus GalactomannanEma Paulovičová0Lucia Paulovičová1Martin Hrubiško2Vadim B. Krylov3Dmitry A. Argunov4Nikolay E. Nifantiev5Cell Culture Laboratory, Department of Immunochemistry of Glycoconjugates, Center for Glycomics, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, SlovakiaCell Culture Laboratory, Department of Immunochemistry of Glycoconjugates, Center for Glycomics, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, SlovakiaDepartment of Clinical Immunology and Allergy, Oncology Institute of St. Elisabeth, Bratislava, SlovakiaLaboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaLaboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, RussiaThe 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 24 h 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01273/fullAspergillusCandidagalactomannanmannanRAW 264.7cytokines
spellingShingle Ema Paulovičová
Lucia Paulovičová
Martin Hrubiško
Vadim B. Krylov
Dmitry A. Argunov
Nikolay E. Nifantiev
Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan
Frontiers in Immunology
Aspergillus
Candida
galactomannan
mannan
RAW 264.7
cytokines
title Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan
title_full Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan
title_fullStr Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan
title_full_unstemmed Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan
title_short Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Aspergillus Galactomannan
title_sort immunobiological activity of synthetically prepared immunodominant galactomannosides structurally mimicking aspergillus galactomannan
topic Aspergillus
Candida
galactomannan
mannan
RAW 264.7
cytokines
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.01273/full
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AT martinhrubisko immunobiologicalactivityofsyntheticallypreparedimmunodominantgalactomannosidesstructurallymimickingaspergillusgalactomannan
AT vadimbkrylov immunobiologicalactivityofsyntheticallypreparedimmunodominantgalactomannosidesstructurallymimickingaspergillusgalactomannan
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