| dc.description |
Single-stranded viral RNA (ssRNA) was recently identified as the natural ligand for TLR7
and TLR8. ssRNA sequences from viruses, as well as their synthetic analogues stimulate
innate immune responses in immune cells from humans and mice, but their
immunostimulatory activity has not been investigated in ruminants. In the present
investigations, we tested whether synthetic RNA oligoribonucleotides (ORN) can activate
immune cells from cattle. In vitro incubation of bovine peripheral blood mononuclear cells
(PBMCs) with ORN-induced production of IL-12, IFN-g and TNF-a. No significant induction
of IFN-a was observed. Depletion of CD14+ cells from PBMC abrogated the IL-12 response
and consequently the IFN-g response, suggesting that CD14+ cells are required for PBMC
immune activation with ORN. Consistent with these findings, the putative receptors for
ORN (TLR7 and TLR8) were expressed at higher levels in the CD14+ fraction than the CD14
PBMC fraction. Pre-treatment of PBMC with bafilomycin (an inhibitor of phagosomal
acidification) prior to stimulation with ORN abolished the cytokine responses, confirming
that the receptor(s) which mediate the ORN-induced responses are intracellular. These
results demonstrate for the first time that the TLR7/8 agonist ORN’s have strong immune
stimulatory effects in cattle, and suggest that further investigation on the potential of
TLR7/8 ligands to activate innate and adaptive immune responses in domestic animals are
warranted. |
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