Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines
Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
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Author to whom correspondence should be addressed.
Academic Editor: Bernhard Ryffel
Cells 2022, 11(1), 134; https://doi.org/10.3390/cells11010134
Received: 28 November 2021
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Revised: 23 December 2021
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Accepted: 27 December 2021
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Published: 1 January 2022
(This article belongs to the Section Cellular Immunology)
Platycodin D (PD) is a potent adjuvant with dual Th1 and Th2 potentiating activity, but its mechanisms of action remain unclear. Here, the C2C12 myoblast cell line and mice were used as in vitro and in vivo models to identify potential signaling pathways involved in the adjuvant activity of PD. PD induced a transient cytotoxicity and inflammatory response in the C2C12 cells and in mouse quadricep muscles. A comparative analysis of microarray data revealed that PD induced similar gene expression profiles in the C2C12 cells and in the quadricep muscles, and triggered rapid regulation of death, immune, and inflammation-related genes, both in vivo and in vitro. It was further demonstrated that caspase-1-dependent pyroptosis was involved in the PD-induced cytotoxicity and inflammatory response in the C2C12 cells via the Ca2+–c-jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)–NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. Consistently, the in vivo analysis revealed that a local blockage of NLRP3 and caspase-1 inhibited PD-induced cytokine production and immune cell recruitment at the injection site, and impaired the adjuvant activity of PD on antigen-specific immune responses to model antigen ovalbumin (OVA) in mice. These findings identified the caspase-1-dependent adjuvanticity of PD and expanded the current knowledge on the mechanisms of action of saponin-based adjuvants.
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Keywords:
platycodin D; adjuvant; pyroptosis; caspase-1; JNK and p38 MAPK signaling; inflammatory response
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MDPI and ACS Style
Zhu, L.; Han, Z.; He, Y.; Sun, H. Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines. Cells 2022, 11, 134. https://doi.org/10.3390/cells11010134
AMA Style
Zhu L, Han Z, He Y, Sun H. Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines. Cells. 2022; 11(1):134. https://doi.org/10.3390/cells11010134
Chicago/Turabian StyleZhu, Liyan, Ziyi Han, Yanfei He, and Hongxiang Sun. 2022. "Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines" Cells 11, no. 1: 134. https://doi.org/10.3390/cells11010134
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