Immunomodulatory properties of mannosylated proteo-liposomes on murine dendritic cells model

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F18%3AN0000217" target="_blank" >RIV/00027162:_____/18:N0000217 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Immunomodulatory properties of mannosylated proteo-liposomes on murine dendritic cells model

Popis výsledku v původním jazyce

Dendritic cells play a crucial role in the immune system. After encountering, engulfing, and processing of an external antigen they are able to elicit CD4+ or CD8+ T cell immune response. CD4+ T cell response is associated with production of neutralizing, opsonizing, complement activating or antibody-dependent cytotoxicity activating antibodies or anaphylaxis inducing antibodies or stimulation of phagocytic cells. In contrast CD8+ T cell immune response is elicited by antigen processed for MHC I presentation which works for intracellular antigens or antigens recognized by DC as exogenous and process by cross-presentation pathway. Such mechanism is responsible for induction of cytotoxic T cells specific to viral or tumor antigens. One of most studied mechanisms inducing cross presentation rely on mannose receptor and its ligand consisting of mannose. In this study the effect of mannosylated nanoliposomes coupled to antigens (mannosylated nanoproteoliposomes) were analyzed in murine bone marrow-derived dendritic cells (BMDCs) model. Two different protein antigens were tested. The Outer surface protein A (OspA) from Borrelia burgdorferi and the envelope protein gp120 from HIV-1 virus. Both proteins were tested alone or bound to liposomes or mannosylated liposomes. Liposomes or proteins were stained with various fluorochromes and used for pulsing BMDCs followed by co-localization with endosomal marker EEA-1 at different time points using confocal fluorescence microscopy. In parallel, BMDC stimulation was measured by flow cytometry using antibody specific to several maturation markers including CD11c, CD80, CD86, MHCI and MHCII. Or results clearly show that BMDC pulsed with antigens coupled to liposomes or mannosylated liposomes were more intensively stimulated than those BMDC pulsed with antigen alone. Moreover high percentage of proteoliposome bound antigen was co-localized with early endosome indicating the ability of proteoliposomes to the force the antigen toward cross-presentation. Furthermore, mannosylated proteoliposomes or liposomes stimulated BMDC to increase expression of activation marker CD80 involved in activatory interaction of DC with naive T cells during the initiation of specific immune response. Our results indicate that poorly immunogenic antigens could be coupled with supporting compounds such as liposomes and mannans to enhance their immunogenicity and to direct antigen toward MHCI presentation and CD8 T cells stimulation.

Název v anglickém jazyce

Immunomodulatory properties of mannosylated proteo-liposomes on murine dendritic cells model

Popis výsledku anglicky

Dendritic cells play a crucial role in the immune system. After encountering, engulfing, and processing of an external antigen they are able to elicit CD4+ or CD8+ T cell immune response. CD4+ T cell response is associated with production of neutralizing, opsonizing, complement activating or antibody-dependent cytotoxicity activating antibodies or anaphylaxis inducing antibodies or stimulation of phagocytic cells. In contrast CD8+ T cell immune response is elicited by antigen processed for MHC I presentation which works for intracellular antigens or antigens recognized by DC as exogenous and process by cross-presentation pathway. Such mechanism is responsible for induction of cytotoxic T cells specific to viral or tumor antigens. One of most studied mechanisms inducing cross presentation rely on mannose receptor and its ligand consisting of mannose. In this study the effect of mannosylated nanoliposomes coupled to antigens (mannosylated nanoproteoliposomes) were analyzed in murine bone marrow-derived dendritic cells (BMDCs) model. Two different protein antigens were tested. The Outer surface protein A (OspA) from Borrelia burgdorferi and the envelope protein gp120 from HIV-1 virus. Both proteins were tested alone or bound to liposomes or mannosylated liposomes. Liposomes or proteins were stained with various fluorochromes and used for pulsing BMDCs followed by co-localization with endosomal marker EEA-1 at different time points using confocal fluorescence microscopy. In parallel, BMDC stimulation was measured by flow cytometry using antibody specific to several maturation markers including CD11c, CD80, CD86, MHCI and MHCII. Or results clearly show that BMDC pulsed with antigens coupled to liposomes or mannosylated liposomes were more intensively stimulated than those BMDC pulsed with antigen alone. Moreover high percentage of proteoliposome bound antigen was co-localized with early endosome indicating the ability of proteoliposomes to the force the antigen toward cross-presentation. Furthermore, mannosylated proteoliposomes or liposomes stimulated BMDC to increase expression of activation marker CD80 involved in activatory interaction of DC with naive T cells during the initiation of specific immune response. Our results indicate that poorly immunogenic antigens could be coupled with supporting compounds such as liposomes and mannans to enhance their immunogenicity and to direct antigen toward MHCI presentation and CD8 T cells stimulation.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/NV15-32198A" target="_blank" >NV15-32198A: Příprava rekombinantních mimotopů indukujících neutralizační protilátky proti HIV-1 gp120 glykoproteinu pomocí technologie vysokoafinitních ligandů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů