Orchestration of Inflammation and Adaptive Immunity in Borrelia burgdorferi–Induced Arthritis by Neutrophil-Activating Protein A
Article first published online: 23 APR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 5, pages 1232–1242, May 2013
How to Cite
Codolo, G., Bossi, F., Durigutto, P., Bella, C. D., Fischetti, F., Amedei, A., Tedesco, F., D'Elios, S., Cimmino, M., Micheletti, A., Cassatella, M. A., D'Elios, M. M. and de Bernard, M. (2013), Orchestration of Inflammation and Adaptive Immunity in Borrelia burgdorferi–Induced Arthritis by Neutrophil-Activating Protein A. Arthritis & Rheumatism, 65: 1232–1242. doi: 10.1002/art.37875
- Issue published online: 23 APR 2013
- Article first published online: 23 APR 2013
- Accepted manuscript online: 31 JAN 2013 11:26AM EST
- Manuscript Accepted: 15 JAN 2013
- Manuscript Received: 25 MAY 2012
- Associazione Italiana per la Ricerca sul Cancro
- Italian Ministry of University and Research
- PRIN Projects
- Fondazione Cariplo. Grant Number: 2011-0485
- Associazione Italiana per la Ricerca sul Cancro fellowship
Lyme arthritis (LA) is characterized by infiltration of inflammatory cells, mainly neutrophils (polymorphonuclear cells [PMNs]) and T cells, into the joints. This study was undertaken to evaluate the role of the neutrophil-activating protein A (NapA) of Borrelia burgdorferi in eliciting inflammation and in driving the adaptive immune response.
Levels of NapA, interferon-γ (IFNγ), interleukin-17 (IL-17), and T cell–attracting chemokines were assessed by enzyme-linked immunosorbent assay in synovial fluid from patients with LA. The profile of T cells recruited into the synovia of patients with LA was defined by fluorescence-activated cell sorting analysis. NapA was intraarticularly injected into rat knees, and the cells recruited in synovia were characterized. The role of NapA in recruiting immune cells was confirmed by chemotaxis assays using a Transwell system.
NapA, IFNγ, IL-17, CCL2, CCL20, and CXCL10 accumulated in synovial fluid from patients with LA. Accordingly, T cells obtained from these patients produced IFNγ or IL-17, but notably, some produced both cytokines. NapA promoted neutrophil and T lymphocyte recruitment both in vitro and in vivo. Interestingly, the infiltration of T cells not only resulted from the chemotactic activity of NapA but also relied on the chemokines produced by PMNs exposed to NapA.
We provide evidence that NapA functions as one of the main bacterial products involved in the pathogenesis of LA. Accordingly, we show that, at very early stages of LA, NapA accumulates and, in turn, orchestrates the recruitment of inflammatory cells into the joint cavity. Thereafter, with the contribution of recruited cells, NapA promotes the infiltration of T cells producing IL-17 and/or IFNγ.