Immune cell response to Candida cell wall mannan derived branched α-oligomannoside conjugates in mice.
BACKGROUND
Constructs composed of cell wall mannan-derived moieties conjugated to immunogenic proteins could be promising agents for induction of protective anti-Candida immune responses.


METHODS
This report is focused on the cellular immune response differences induced by BSA-based conjugates bearing synthetic α-1,6-branched oligomannosides. For monitoring of the immune responses following active immunization we evaluated changes in the frequencies of T and B lymphocytes and their activation status in the blood and spleen. We compared the immunization-induced changes of co-stimulatory molecules CD80 and CD86 expression on blood neutrophils and Th1/Th2 polarization of the immune response based on IFN-γ, TNF-α (pro-Th1), IL-4, and IL-10 (pro-Th2) cytokines levels and induction of IL-17.


RESULTS
The results pointed out a comparable effect of the conjugates on the modulation of T and B lymphocytes frequencies in blood and spleen. Both conjugates induced upregulation of CD25 surface antigen on CD4(+) T lymphocytes, independently on the structural differences of oligosaccharides. The differences in structure of oligomannoside antigens or conjugate constructs were reflected in the increase of co-stimulatory molecules CD80 and CD86 expression on neutrophils, and in induced cytokine response. M5-BSA conjugate induced only a slight increase in CD80 expression but a significant increase in IFN-γ, TNF-α, and IL-10. M6-BSA conjugate induced a significant increase of CD80 expression and increase of TNF-α, IL-4, and IL-10.


CONCLUSIONS
Obtained data demonstrate the importance of cellular immune response analysis for investigation of immunomodulatory properties of oligomannoside-protein conjugates.
Institute of Chemistry, Department of Immunochemistry of Glycoconjugates, Centre of Excellence Glycomed, Slovak Academy of Sciences, Bratislava, Slovakia. Electronic address: chemluli@savba.sk.
Lucia
L
Paulovičová
Institute of Chemistry, Department of Immunochemistry of Glycoconjugates, Centre of Excellence Glycomed, Slovak Academy of Sciences, Bratislava, Slovakia.
Ema
E
Paulovičová
N.D. Zelinsky Institute of Organic Chemistry, Laboratory of Glycoconjugate Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.
Alexander A
AA
Karelin
N.D. Zelinsky Institute of Organic Chemistry, Laboratory of Glycoconjugate Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.
Yury E
YE
Tsvetkov
N.D. Zelinsky Institute of Organic Chemistry, Laboratory of Glycoconjugate Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.
Nikolay E
NE
Nifantiev
Institute of Chemistry, Department of Immunochemistry of Glycoconjugates, Centre of Excellence Glycomed, Slovak Academy of Sciences, Bratislava, Slovakia.
Slavomír
S
Bystrický
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D002175:Candida / Q000737:chemistry / Q000276:immunology*; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016130:Immunophenotyping; D008351:Mannans / Q000276:immunology* / Q000302:isolation & purification; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D009844:Oligosaccharides / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D005657:Fungal Vaccines; D008351:Mannans; D009844:Oligosaccharides; D018074:Vaccines, Conjugate; C028569:oligomannoside
Candida albicans; Cellular immunity; Immunomodulation; Mannan-derived glycoconjugates; Oligomannoside