mannan Dotaz Zobrazit nápovědu
Candida glabrata is a second most common human opportunistic pathogen which causes superficial but also life-threatening systemic candidosis. According to the localisation of mannans and mannoproteins in the outermost layer of the cell wall, mannan detection could be one of the first steps in the cell recognition of Candida cells by the host innate immune system. Mannans from the cell wall provide important immunomodulatory activities, comprising stimulation of cytokine production, induction of dendritic cells (DCs) maturation and T-cell immunity. The model of DCs represents a promising tool to study immunomodulatory interventions throughout the vaccine development. Activated DCs induce, activate and polarise T-cell responses by expression of distinct maturation markers and cytokines regulating the adaptive immune responses. In addition, they are uniquely adept at decoding the fungus-associated information and translate it in qualitatively different T helper responses. We find out, that C. glabrata mannan is able to induce proliferation of splenocytes and to increase the production of TNF-α and IL-4. Next, increased the expression of co-stimulatory molecules CD80 and CD86 and the proportion of CD4+CD25+ and CD4+CD28+ T cells during in vitro stimulation of splenocytes. Reported results provide C. glabrata mannan capability to modulate cytokine production, DCs activation and antigen presentation activity, influencing T-cell phenotype in response to stimulation.
- MeSH
- Candida glabrata imunologie MeSH
- cytokiny metabolismus MeSH
- dendritické buňky imunologie MeSH
- imunologické faktory metabolismus MeSH
- kultivované buňky MeSH
- mannany metabolismus MeSH
- myši MeSH
- přirozená imunita * MeSH
- proliferace buněk účinky léků MeSH
- T-lymfocyty imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- kvasinky fyziologie MeSH
- lidé MeSH
- mannany biosyntéza MeSH
- Check Tag
- lidé MeSH
New synthetic aminooxy lipid was designed and synthesized as a building block for the formulation of functionalised nanoliposomes (presenting onto the outer surface of aminooxy groups) by microfluidic mixing. Orthogonal binding of cellular mannan (Candida glabrata (CCY 26-20-1) onto the outer surface of functionalised nanoliposomes was modified by orthogonal binding of reducing termini of mannans to oxime lipids via a click chemistry reaction based on aminooxy coupling (oxime ligation). The aminooxy lipid was proved as a suitable active component for preparation of functionalised nanoliposomes by the microfluidic mixing method performed with the instrument NanoAssemblrTM. This "on-chip technology" can be easily scaled-up. The structure of mannan-liposomes was visualized by transmission and scanning electron microscopy, including immunogold staining of recombinant mannan receptor bound onto mannosylated-liposomes. The observed structures are in a good correlation with data obtained by DLS, NTA, and TPRS methods. In vitro experiments on human and mouse dendritic cells demonstrate selective internalisation of fluorochrome-labelled mannan-liposomes and their ability to stimulate DC comparable to lipopolysaccharide. We describe a potentially new drug delivery platform for mannan receptor-targeted antimicrobial drugs as well as for immunotherapeutics. Furthermore, the platform based on mannans bound orthogonally onto the surface of nanoliposomes represents a self-adjuvanted carrier for construction of liposome-based recombinant vaccines for both systemic and mucosal routes of administration.
- MeSH
- adjuvancia imunologická farmakologie MeSH
- antigeny povrchové metabolismus MeSH
- Candida glabrata chemie MeSH
- dendritické buňky imunologie MeSH
- hydroxylaminy chemická syntéza chemie MeSH
- lektiny typu C imunologie MeSH
- lektiny vázající mannosu imunologie MeSH
- lidé MeSH
- lipidy chemická syntéza chemie MeSH
- liposomy chemie imunologie farmakologie MeSH
- mannany chemie imunologie farmakologie MeSH
- mikrofluidika metody MeSH
- myši inbrední BALB C MeSH
- nanočástice chemie MeSH
- receptory buněčného povrchu imunologie MeSH
- syntetická chemie okamžité shody MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
