To study the functional impact of the L412F variant of TLR3 we tested patients' peripheral blood mononuclear cells (PBMCs) as well as fibroblasts for secretion of cytokines in response to TLR3 ligand, candida or cytomegalovirus (CMV). In addition, the P2.1 cell line was used as a model for the TLR3 WT and L412F variant receptors function.
Patient's cells carrying the L412F variant showed reduced IFN纬 as well as TNF伪 secretion in response to stimulation with the TLR3 ligand, CMV or Candida albicans. Fibroblasts with the L412F variant showed decreased secretion of IFN位 in response to stimulation with both polyinosine ploycytidylic acid (Poly I:C) and CMV and P2.1 cells transfected with the L412F variant showed reduced secretion of IFN-尾 in comparison to cells transfected with the wild type receptor.
We have shown here aberrant biological responses mediated by the TLR3 variant receptor, L412F, which may explain in part susceptibility of patients to chronic candidiasis, viral infections and autoimmunity.