Borrelia burgdorferi NapA–driven Th17 cell inflammation in lyme arthritis

Objective Human Lyme arthritis caused by Borrelia burgdorferi is characterized by an inflammatory infiltrate that consists mainly of neutrophils and T cells. This study was undertaken to evaluate the role of the innate and acquired immune responses elicited by the neutrophil‐activating protein A (NapA) of B burgdorferi in patients with Lyme arthritis. Methods Serum anti‐NapA antibodies were measured in 27 patients with Lyme arthritis and 30 healthy control subjects. The cytokine profile of synovial fluid T cells specific for NapA was investigated in 5 patients with Lyme arthritis. The cytokine profile induced by NapA in neutrophils and monocytes was also investigated. Results Serum anti‐NapA antibodies were found in 48% of the patients with Lyme arthritis but were undetectable in the healthy controls. T cells from the synovial fluid of patients with Lyme arthritis produced interleukin‐17 (IL‐17) in response to NapA. Moreover, NapA was able to induce the expression of IL‐23 in neutrophils and monocytes, as well as the expression of IL‐6, IL‐1β, and transforming growth factor β (TGFβ) in monocytes, via Toll‐like receptor 2. Conclusion These findings indicate that NapA of B burgdorferi is able to drive the expression of IL‐6, IL‐1β, IL‐23, and TGFβ by cells of the innate immune system and to elicit a synovial fluid Th17 cell response that might play a crucial role in the pathogenesis of Lyme arthritis.