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Stimulation of Innate and Adaptive Immunity by Using Filamentous Bacteriophage fd Targeted to DEC-205.

D'Apice L, Costa V, Sartorius R, Trovato M, Aprile M, De Berardinis P - J Immunol Res (2015)

Bottom Line: The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants.By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd.RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Biochemistry (IBP), National Council of Research, 80131 Naples, Italy.

ABSTRACT
The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants. By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd. RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.

No MeSH data available.


Related in: MedlinePlus

Interferon signature in genes modulated by fdsc-αDEC. (a) Venn diagram of the genes analyzed by INTERFEROME 2.0 database. (b) Heatmap of 183 “interferon-related” genes modulated upon fdsc-αDEC treatment. Expression values are indicated as logRPKM (reads per kilobase of transcript per million of mapped reads). (c) Heatmap obtained using the online Pscan tool indicating the presence (in red) of transcription factors binding sites (TFBS) within promoters of a selected gene list. In the red box on the left, a detail of such computational analysis is shown.
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fig5: Interferon signature in genes modulated by fdsc-αDEC. (a) Venn diagram of the genes analyzed by INTERFEROME 2.0 database. (b) Heatmap of 183 “interferon-related” genes modulated upon fdsc-αDEC treatment. Expression values are indicated as logRPKM (reads per kilobase of transcript per million of mapped reads). (c) Heatmap obtained using the online Pscan tool indicating the presence (in red) of transcription factors binding sites (TFBS) within promoters of a selected gene list. In the red box on the left, a detail of such computational analysis is shown.

Mentions: The genes whose expression was significantly modulated after fdsc–αDEC treatment in dendritic cells were analyzed using the INTERFEROME 2.0 database. The analysis revealed the presence of a clear transcriptional interferon signature. Notably, 183 genes out of 361 significantly (FDR < 0.0005) DEG (about 50%) are modulated by Interferon Regulated Factors (IRFs) or by the NF-kB transcription factors and possess Interferon-Stimulated Response Elements (ISREs). The Venn diagram in Figure 5(a) illustrates how many DE genes are regulated per interferon type. In detail, 73 out of 183 genes are IFN Type-I dependent, 26 are type-II dependent, and 84 are regulated by both interferons. Expression levels of interferon-regulated genes in DCs, in presence or absence of fdsc-αDEC, are shown in the heatmap of Figure 5(b). In addition, we decided to assess whether genes that are affected by fdsc-αDEC treatment in DCs have a specific transcription factor binding sites (TFBS) signature within their promoters. To this aim, using Pscan we found that most of upregulated genes have ISREs and binding sites for IRF1, IRF2, and IRF7 molecules (Figure 5(c)). Interestingly, among them are included genes coding for cytokines and chemokines, transcriptional regulators, DNA binding proteins, proteins involved in ISGylation and ubiquitination, and proteins with a known activity in the innate anti-viral response and immune activation (details in Table 1).


Stimulation of Innate and Adaptive Immunity by Using Filamentous Bacteriophage fd Targeted to DEC-205.

D'Apice L, Costa V, Sartorius R, Trovato M, Aprile M, De Berardinis P - J Immunol Res (2015)

Interferon signature in genes modulated by fdsc-αDEC. (a) Venn diagram of the genes analyzed by INTERFEROME 2.0 database. (b) Heatmap of 183 “interferon-related” genes modulated upon fdsc-αDEC treatment. Expression values are indicated as logRPKM (reads per kilobase of transcript per million of mapped reads). (c) Heatmap obtained using the online Pscan tool indicating the presence (in red) of transcription factors binding sites (TFBS) within promoters of a selected gene list. In the red box on the left, a detail of such computational analysis is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Interferon signature in genes modulated by fdsc-αDEC. (a) Venn diagram of the genes analyzed by INTERFEROME 2.0 database. (b) Heatmap of 183 “interferon-related” genes modulated upon fdsc-αDEC treatment. Expression values are indicated as logRPKM (reads per kilobase of transcript per million of mapped reads). (c) Heatmap obtained using the online Pscan tool indicating the presence (in red) of transcription factors binding sites (TFBS) within promoters of a selected gene list. In the red box on the left, a detail of such computational analysis is shown.
Mentions: The genes whose expression was significantly modulated after fdsc–αDEC treatment in dendritic cells were analyzed using the INTERFEROME 2.0 database. The analysis revealed the presence of a clear transcriptional interferon signature. Notably, 183 genes out of 361 significantly (FDR < 0.0005) DEG (about 50%) are modulated by Interferon Regulated Factors (IRFs) or by the NF-kB transcription factors and possess Interferon-Stimulated Response Elements (ISREs). The Venn diagram in Figure 5(a) illustrates how many DE genes are regulated per interferon type. In detail, 73 out of 183 genes are IFN Type-I dependent, 26 are type-II dependent, and 84 are regulated by both interferons. Expression levels of interferon-regulated genes in DCs, in presence or absence of fdsc-αDEC, are shown in the heatmap of Figure 5(b). In addition, we decided to assess whether genes that are affected by fdsc-αDEC treatment in DCs have a specific transcription factor binding sites (TFBS) signature within their promoters. To this aim, using Pscan we found that most of upregulated genes have ISREs and binding sites for IRF1, IRF2, and IRF7 molecules (Figure 5(c)). Interestingly, among them are included genes coding for cytokines and chemokines, transcriptional regulators, DNA binding proteins, proteins involved in ISGylation and ubiquitination, and proteins with a known activity in the innate anti-viral response and immune activation (details in Table 1).

Bottom Line: The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants.By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd.RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.

View Article: PubMed Central - PubMed

Affiliation: Institute of Protein Biochemistry (IBP), National Council of Research, 80131 Naples, Italy.

ABSTRACT
The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC-205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants. By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd. RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response.

No MeSH data available.


Related in: MedlinePlus