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Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.

Szpakowski P, Biet F, Locht C, Paszkiewicz M, Rudnicka W, Druszczyńska M, Allain F, Fol M, Pestel J, Kowalewicz-Kulbat M - J Immunol Res (2015)

Bottom Line: We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective.In contrast, both BCG strains decreased the DC-SIGN expression on human DCs.The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.

ABSTRACT
Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4(+) T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

No MeSH data available.


Related in: MedlinePlus

Secretion of  IFN-γ by human naive and memory T cells following 24 h and 96 h coculture with BCG- (1 : 1), rBCGIL-18- (1 : 1) pulsed autologous MoDCs (ratio MoDCs/T cells, 1 : 10) in the presence (black bars) of neutralizing human anti-IL-18 antibody or not (grey bars). The cytokine level in the cocultures was measured by ELISA. One representative experiment out of three independent ones is shown.
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Related In: Results  -  Collection


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fig8: Secretion of  IFN-γ by human naive and memory T cells following 24 h and 96 h coculture with BCG- (1 : 1), rBCGIL-18- (1 : 1) pulsed autologous MoDCs (ratio MoDCs/T cells, 1 : 10) in the presence (black bars) of neutralizing human anti-IL-18 antibody or not (grey bars). The cytokine level in the cocultures was measured by ELISA. One representative experiment out of three independent ones is shown.

Mentions: The IL-18 specificity of rBCGhIL-18-driven enhancement of IFN-γ production in DC-naive T cell cocultures was demonstrated in the anti-IL-18 neutralizing experiments conducted for three individuals (Figure 8). As shown in Figure 8, in the presence of the human anti-IL-18 antibody, the production of IFN-γ by naive T cells was reduced in response to rBCGhIL-18-stimulated DC coincubation, both after 24 and 96 h of culture; this was much less the case for rBCGhIL-18-stimulated DC-memory T cell cultures.


Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.

Szpakowski P, Biet F, Locht C, Paszkiewicz M, Rudnicka W, Druszczyńska M, Allain F, Fol M, Pestel J, Kowalewicz-Kulbat M - J Immunol Res (2015)

Secretion of  IFN-γ by human naive and memory T cells following 24 h and 96 h coculture with BCG- (1 : 1), rBCGIL-18- (1 : 1) pulsed autologous MoDCs (ratio MoDCs/T cells, 1 : 10) in the presence (black bars) of neutralizing human anti-IL-18 antibody or not (grey bars). The cytokine level in the cocultures was measured by ELISA. One representative experiment out of three independent ones is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539176&req=5

fig8: Secretion of  IFN-γ by human naive and memory T cells following 24 h and 96 h coculture with BCG- (1 : 1), rBCGIL-18- (1 : 1) pulsed autologous MoDCs (ratio MoDCs/T cells, 1 : 10) in the presence (black bars) of neutralizing human anti-IL-18 antibody or not (grey bars). The cytokine level in the cocultures was measured by ELISA. One representative experiment out of three independent ones is shown.
Mentions: The IL-18 specificity of rBCGhIL-18-driven enhancement of IFN-γ production in DC-naive T cell cocultures was demonstrated in the anti-IL-18 neutralizing experiments conducted for three individuals (Figure 8). As shown in Figure 8, in the presence of the human anti-IL-18 antibody, the production of IFN-γ by naive T cells was reduced in response to rBCGhIL-18-stimulated DC coincubation, both after 24 and 96 h of culture; this was much less the case for rBCGhIL-18-stimulated DC-memory T cell cultures.

Bottom Line: We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective.In contrast, both BCG strains decreased the DC-SIGN expression on human DCs.The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.

ABSTRACT
Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4(+) T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

No MeSH data available.


Related in: MedlinePlus