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

被引:12
作者
Awate, Sunita [1 ,2 ]
Eng, Nelson F. [2 ]
Gerdts, Volker [2 ,3 ]
Babiuk, Lorne A. [4 ]
Mutwiri, George [1 ,2 ]
机构
[1] Univ Saskatchewan, Sch Publ Hlth, Vaccinol & Immunotherapeut Program, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada
[2] Vaccine & Infect Dis Org, Int Vaccine Ctr, Saskatoon, SK S7N 5E3, Canada
[3] Univ Saskatchewan, Western Coll Vet Med, Dept Vet Microbiol, Saskatoon, SK S7N 5B4, Canada
[4] Univ Alberta, Edmonton, AB T6G 2J9, Canada
来源
VACCINES | 2014年 / 2卷 / 03期
基金
加拿大自然科学与工程研究理事会;
关键词
adjuvants; polyphosphazenes; inflammasomes; IL-1; beta; T-cells;
D O I
10.3390/vaccines2030500
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 beta and IL-18, in mouse muscle tissue. Caspase-1 is required for the processing of pro-forms of IL-1 beta 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-1 beta and IL-18 in PCEP-stimulated splenic dendritic cells (DCs). Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1 beta 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-gamma by CD4(+) and CD8(+) T-cells. We conclude that PCEP activates innate immunity, leading to increased antigen-specific T-cell responses.
引用
收藏
页码:500 / 514
页数:15
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