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-1beta, and transforming growth factor beta (TGFbeta) in monocytes, via Toll-like receptor 2.


CONCLUSIONS
These findings indicate that NapA of B burgdorferi is able to drive the expression of IL-6, IL-1beta, IL-23, and TGFbeta 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.
Codolo
Gaia
G
Venetian Institute of Molecular Medicine, and University of Padua, Padua, Italy.
Amedei
Amedeo
A
Steere
Allen C
AC
Papinutto
Elena
E
Cappon
Andrea
A
Polenghi
Alessandra
A
Benagiano
Marisa
M
Paccani
Silvia Rossi
SR
Sambri
Vittorio
V
Del Prete
Gianfranco
G
Baldari
Cosima Tatiana
CT
Zanotti
Giuseppe
G
Montecucco
Cesare
C
D'Elios
Mario Milco
MM
de Bernard
Marina
M
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis; D001426:Bacterial Proteins / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D019743:Chemokines, CXC / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008193:Lyme Disease / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D019743:Chemokines, CXC; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; C534091:NapA protein, Borrelia burgdorferi; D016212:Transforming Growth Factor beta