Orchestration of inflammation and adaptive immunity in borrelia burgdorferi-induced arthritis by neutrophil-activating protein A

Gaia Codolo, Fleur Bossi, Paolo Durigutto, Chiara Della Bella, Fabio Fischetti, Amedeo Amedei, Francesco Tedesco, Sofia D'Elios, Marco Cimmino, Alessandra Micheletti, Marco A. Cassatella, Mario M. D'Elios, Marina De Bernard

Research output: Contribution to journalArticle

Abstract

Objective 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. Methods 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. Results 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. Conclusion 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.

Original languageEnglish
Pages (from-to)1232-1242
Number of pages11
JournalArthritis and Rheumatism
Volume65
Issue number5
DOIs
Publication statusPublished - May 2013

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Orchestration of inflammation and adaptive immunity in borrelia burgdorferi-induced arthritis by neutrophil-activating protein A'. Together they form a unique fingerprint.

Cite this