Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP
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 NLR...
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MDPI AG
2014-06-01
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| Series: | Vaccines |
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| Online Access: | http://www.mdpi.com/2076-393X/2/3/500 |
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| author | Sunita Awate Nelson F. Eng Volker Gerdts Lorne A. Babiuk George Mutwiri |
| author_facet | Sunita Awate Nelson F. Eng Volker Gerdts Lorne A. Babiuk George Mutwiri |
| author_sort | Sunita Awate |
| collection | DOAJ |
| description | 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 that PCEP activates innate immunity, leading to increased antigen-specific T-cell responses. |
| first_indexed | 2024-04-11T12:44:08Z |
| format | Article |
| id | doaj.art-525c79f804e84a9585dac6bc206bbe2c |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T12:44:08Z |
| publishDate | 2014-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-525c79f804e84a9585dac6bc206bbe2c2022-12-22T04:23:24ZengMDPI AGVaccines2076-393X2014-06-012350051410.3390/vaccines2030500vaccines2030500Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEPSunita Awate0Nelson F. Eng1Volker Gerdts2Lorne A. Babiuk3George Mutwiri4Vaccinology and Immunotherapeutics program, School of Public Health, 107 Wiggins Road, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaVaccine and Infectious Disease Organization-International Vaccine Centre, 120 Veterinary Road, University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaVaccine and Infectious Disease Organization-International Vaccine Centre, 120 Veterinary Road, University of Saskatchewan, Saskatoon, SK S7N 5E3, CanadaUniversity of Alberta, 3-7 University Hall, Edmonton, AB T6G 2J9, CanadaVaccinology and Immunotherapeutics program, School of Public Health, 107 Wiggins Road, University of Saskatchewan, Saskatoon, SK S7N 5E5, CanadaThe 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 that PCEP activates innate immunity, leading to increased antigen-specific T-cell responses.http://www.mdpi.com/2076-393X/2/3/500adjuvantspolyphosphazenesinflammasomesIL-1βT-cells |
| spellingShingle | Sunita Awate Nelson F. Eng Volker Gerdts Lorne A. Babiuk George Mutwiri Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP Vaccines adjuvants polyphosphazenes inflammasomes IL-1β T-cells |
| title | Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP |
| title_full | Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP |
| title_fullStr | Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP |
| title_full_unstemmed | Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP |
| title_short | Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP |
| title_sort | caspase 1 dependent il 1β secretion and antigen specific t cell activation by the novel adjuvant pcep |
| topic | adjuvants polyphosphazenes inflammasomes IL-1β T-cells |
| url | http://www.mdpi.com/2076-393X/2/3/500 |
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