Evaluation of immunostimulatory potential of synthetic TLR2 agonists in chicken

The ligands of toll like receptor (TLR) have great potential as vaccine adjuvants. TLR activation causes effector responses such as the synthesis of cytokines and chemokines, the generation of interferons etc. Synthetic TLR2 agonists have been successfully used as experimental vaccine adjuvant in both mammals and chicken. However, their low solubility, high cost and detrimental effect towards protein antigen limits its wider application. Present study was aimed to screen out few synthetic TLR2 agonists for its immunostimulatory potential using chicken peripheral blood mononuclear cells (PBMCs). Total of five synthetic lipopeptide based TLR2 agonists (P1, P2, P6, P7 and P8) have been evaluated for their potential to induce the expression of immune response genes in chicken PBMCs. Each agonist significantly upregulated the expression of IL-1β and iNOS at 3h post-treatment with highest expression of IL-1β mRNA was observed with P1. There was a significant up-regulation of IFN-β and IFN-γ by treatment with P1 at 3 and 12h intervals ( p <0.05). Further, IL-4 mRNA was significantly upregulated with P1 and P7 treatment at 12 and 24h post-treatment respectively. Our results demonstrate that among all five agonists, P1 was superior in terms of up-regulation of immune response genes such as both type I and type II interferons along with mixed Th1 and Th2 responses.