Confirming the role of type I IFN in limiting virus replication. Human IFNa has been shown to effectively suppress the replication of bovine viral diarrhea virus and bovine parainfluenza virus. Cytokines play a pivotal role in the induction and modulation of immunological responses. TLR signaling events lead to the activation of nuclear factor kapp-light-chain-enhancer of activated B cells and interferon regulatory factor, which switch on Afatinib 439081-18-2 expression of a specific panel of pro-inflammatory cytokines and chemokines such as TNFa, IL6, IL8 and Regulated on activation, Normal T cells. Activation of TLR by viruses also results in the production and release of type I IFNs. TLR3 and TLR7 engagement by synthetic ligands lead to cytokine expression profiles similar to PPRV infection except for a weak IL1b, IL6 and IL8 production in goat PBMC. A predominantly inflammatory cytokine repertoire, with expression of TNFa, IFNa and IFNc was observed at both mRNA and protein levels. Thus, it could be inferred that TLR engagement upon PPRV infection results in inflammatory cytokine production via the canonical NFkB pathway and type I IFN production via the activation of IRFs. Stimulation of TLR7 with synthetic RNA oligonucleotides has earlier been shown to induce production of IL-12, TNFa and IFNc in PBMC of cattle. Interestingly, in our study, IFNc levels were higher in PPRV infected PBMC, compared to the engagement of TLR3/7 by their respective agonists. IFNc production by NK cells can be induced by IL12 secreted by TLR stimulated DCs. In buffalos, approximately 1.5 fold higher levels of IFNa at mRNA and protein levels were induced in PBMC compared to goats after infection with PPRV suggesting that type I IFN may play a role in limiting virus replication in buffalo. Further, we found that TLR7 mediated IFNa production is critical because TLR7 antagonist inhibited IFNa production both in Imiquimod or PPRV-treated goat and buffalo PBMC. This effect was more prominent in buffalo PBMC suggesting that TLR7 mediated IFNa production determines PPRV replication efficiency in this species. Consistent with the inflammatory cytokine environment induced by PPRV infection, expression of the immunomodulatory cytokine IL10 was also observed, but its levels were high in the PPRV susceptible goat breeds, Barbari and Tellicherry. IL10 is a key regulatory cytokine with immunosuppressive properties that helps to regulate an uncontrolled inflammatory response. In addition to preventing the maturation of antigen presenting cells, IL10 can also regulate the proliferation and differentiation of Th1 cells, which induces T cell-dependent suppression of antiviral responses. Dexamethasone, a well-known immunosuppressive drug, induces immunosuppression by altering the expression levels of IL10 and TNFa. Experimental immunosuppression of goat with dexamethasone and challenge with virulent PPRV indicated.