Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP

Vaccines
Sunita AwateGeorge Mutwiri

Abstract

The potent adjuvant activity of the novel adjuvant, poly[di(sodiumcarboxylatoethylphenoxy)phosphazene] (PCEP), with various antigens has been reported previously. However, very little is known about its mechanisms of action. We have recently reported that intramuscular injection of PCEP induces NLRP3, an inflammasome receptor gene, and inflammatory cytokines, including IL-1β and IL-18, in mouse muscle tissue. Caspase-1 is required for the processing of pro-forms of IL-1β and IL-18 into mature forms and is a critical constituent of the NLRP3 inflammasome. Hence, in the present study, we investigated the role of caspase-1 in the secretion of IL-1β and IL-18 in PCEP-stimulated splenic dendritic cells (DCs). Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1β and IL-18 secretion in response to PCEP stimulation. Further, PCEP had no effect on the expression of MHC class II or co-stimulatory molecules, CD86 and CD40, suggesting that PCEP does not induce DC maturation. However, PCEP directly activated B-cells to induce significant production of IgM. In addition, PCEP+ovalbumin (OVA) immunized mice showed significantly increased production of antigen-specific IFN-γ by CD4⁺ and CD8⁺ T-cells. We conclude tha...Continue Reading

References

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Apr 24, 2012·Molecular Immunology·Sunita AwateGeorge Mutwiri

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Citations

Oct 9, 2018·Cell and Tissue Research·Royford MagiriHeather L Wilson
Oct 7, 2020·Vaccines·Azita HaddadiHeather L Wilson
Dec 8, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alexander K Andrianov, Robert Langer
Mar 26, 2021·Frontiers in Bioengineering and Biotechnology·Dylan J ChandGeorge K Mutwiri

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Methods Mentioned

BETA
flow cytometry
ELISA
electrophoresis
Assay

Software Mentioned

GraphPad
GraphPad Prism

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