RNA-seq analysis of PBMCs with TLR1-1805TT and TLR1-1805GG genotypes stimulated and restimulated (innate immune tolerance induction) with B. burgdorferi.

A TLR1 variant (1805GG) associated with severe Lyme disease may drive excessive inflammation. To investigate this, we stimulated (16hr) and restimulated (6hr) PBMCs from donors with or without TLR1-1805GG using Borrelia burgdorferi. Variant carriers showed stronger transcriptional and cytokine responses and failed to develop innate immune tolerance upon restimulation, indicating dysregulated inflammation that may underlie persistent disease.