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Volume 48, Number 1, February 2015

Immune cell response to Candida cell wall mannan derived branched α-oligomannoside conjugates in mice 


Lucia Paulovičová, Ema Paulovičová, Alexander A. Karelin, Yury E. Tsvetkov, Nikolay E. Nifantiev, Slavomír Bystrický


Received: July 31, 2013    Revised: August 20, 2013    Accepted: August 26, 2013   

 

Background and purpose: 

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. 



 

Conclusion:

Obtained data demonstrate the importance of cellular immune response analysis for investigation of immunomodulatory properties of oligomannoside–protein conjugates. 



 

Key words:

Candida albicans, Cellular immunity, Immunomodulation, Mannan-derived glycoconjugates, Oligomannoside