The adjuvant G3 promotes a Th1 polarizing innate immune response in equine PBMC.
Abstract: The immunomodulatory effect of a new particulate adjuvant, G3, alone or in combination with agonists to TLR2/1 or TLR5 was evaluated in cultures of equine PBMC. Exposure to the G3 adjuvant up-regulated genes encoding IFN-γ, IL-1β, IL-6, IL-8, IL-12p40 and IL-23p19 in the majority of the horses tested, indicating that the G3 adjuvant induced a pro-inflammatory and Th1 dominated profile. In accordance, genes encoding IL-13, IL-4, IL-10 and TGF-β remained unaffected and genes encoding IFN-α, IL-17A and TNF-α were only occasionally and weakly induced. The two TLR agonists Pam3CSK4 (TLR2/1) and FliC (TLR5) induced cytokine profiles characterized by a clear induction of IL-10 as well as up-regulation of the genes encoding IL-1β, IL-6 and IL-8. The presence of G3 modified this response, in particular by reducing the FliC and Pam3CSK4 induced production of IL-10. Furthermore, G3 acted in synergy with Pam3CSK4 in enhancing the production of IFN-γ whereas G3 combined with FliC increased the gene expression of IL-8. Thus, the G3 adjuvant seems to have the capacity to promote a Th1 polarizing innate immune response in eqPBMC, both by favouring IFN-γ production and by reducing production of IL-10 induced by co-delivered molecules. These features make G3 an interesting candidate to further evaluate for its potential as an adjuvant in equine vaccines.
Publication Date: 2018-10-22 PubMed ID: 30348190PubMed Central: PMC6389152DOI: 10.1186/s13567-018-0602-2Google Scholar: Lookup
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- Journal Article
Summary
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The research investigates the impact of a new adjuvant, G3, on the innate immune response in horses, particularly its ability to promote Th1 (Type 1 helper T cells) polarization and its potential as a vaccine ingredient.
Study Overview
- The study explored the immunomodulatory effect of a new particulate adjuvant, dubbed G3, alone or in combination with agonists to TLR2/1 (Toll-like Receptor 2 and 1) or TLR5 (Toll-like Receptor 5). The effect of the G3 adjuvant was evaluated in cultures of equine peripheral blood mononuclear cells (PBMC).
Findings on G3 Adjuvant
- Upon being exposed to the G3 Adjuvant, the expression of several genes, including those that encode IFN-γ, IL-1β, IL-6, IL-8, IL-12p40, and IL-23p19 was up-regulated in majority of the horses that were tested in the study. This implies that the G3 adjuvant promotes a pro-inflammatory and Th1 dominated immune profile.
- Other genes, such as those encoding IL-13, IL-4, IL-10, and TGF-β, did not seem to be affected with exposure to the G3 adjuvant, while the expression of genes encoding IFN-α, IL-17A, and TNF-α were only mildly induced sometimes.
Findings on TLR Agonists and G3 Adjuvant
- TLR agonists Pam3CSK4 (TLR2/1) and FliC (TLR5) brought about cytokine profiles characterized by clear induction of IL-10 and the up-regulation of genes encoding IL-1β, IL-6, and IL-8.
- Introduction of the G3 adjuvant altered this response with notable reduction in FLiC and Pam3CSK4-induced production of IL-10.
- G3 also appeared to act synergistically with Pam3CSK4, increasing the production of IFN-γ. In combination with FliC, G3 upped gene expression of IL-8.
Conclusion
- The G3 adjuvant shows promise in its capacity to drive a Th1 polarizing innate immune response in the equine PBMC. This is seen in its preference for IFN-γ production and its ability to curtail production of IL-10 induced by co-delivered molecules.
- The observed characteristics of G3 adjuvant make it a strong candidate worth evaluating for its potential use as an adjuvant in equine vaccines.
Cite This Article
APA
Hellman S, Hjertner B, Morein B, Fossum C.
(2018).
The adjuvant G3 promotes a Th1 polarizing innate immune response in equine PBMC.
Vet Res, 49(1), 108.
https://doi.org/10.1186/s13567-018-0602-2 Publication
Researcher Affiliations
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SLU, Box 7028, 750 07, Uppsala, Sweden. Stina.Hellman@slu.se.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SLU, Box 7028, 750 07, Uppsala, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SLU, Box 7028, 750 07, Uppsala, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SLU, Box 7028, 750 07, Uppsala, Sweden.
MeSH Terms
- Adjuvants, Immunologic / pharmacology
- Animals
- Cytokines / genetics
- Cytokines / metabolism
- Female
- Gene Expression Regulation / drug effects
- Gene Expression Regulation / immunology
- Horses / blood
- Horses / immunology
- Immunity, Innate / drug effects
- Leukocytes, Mononuclear / physiology
- Lipopeptides / pharmacology
- Male
- Toll-Like Receptors
Grant Funding
- H-16-47-193 / Swedish-Norwegian Foundation for Equine Research
- GFS2015-0140 / Royal Swedish Academy of Agriculture and Forestry
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Citations
This article has been cited 5 times.- Lee DH, Lee EB, Seo JP, Ko EJ. In vitro effects of monophosphoryl lipid A and Poly I:C combination on equine cells.. J Vet Sci 2023 May;24(3):e37.
- Carnet F, Perrin-Cocon L, Paillot R, Lotteau V, Pronost S, Vidalain PO. An inventory of adjuvants used for vaccination in horses: the past, the present and the future.. Vet Res 2023 Mar 2;54(1):18.
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