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Neutrophil hyperchemotaxis in Behçet’s disease: a possible role for monocytes orchestrating bacterial-induced innate immune responses

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Abstract

Increased neutrophil chemotaxis and hyperresponsiveness to streptococci have been considered to play a role in Behçet’s disease (BD) pathogenesis. Our aim was to correlate TLR2 expression and chemotactic responses stimulated by bacterial lipoteichoic acid (LTA) in BD neutrophils. Thus, we assessed expressions of TLR2 and the correlate receptors CD14, CD114 (G-CSF receptor), CD116 (GM-CSF receptor) and also TLR4 on circulating neutrophils and monocytes of patients with active BD. Serum concentration of soluble CD14 (sCD14) was also measured. Neutrophil chemotactic responses from BD patients and healthy controls under LTA stimulation were assessed. Disease activity was evaluated by Behçet’s Disease Current Activity Form (BDCAF). Receptor expressions were measured by flow cytometry, neutrophil chemotaxis was assessed in a Boyden chamber and sCD14 was measured by enzyme-linked immunosorbent assay. TLR2 expression was higher only on BD monocytes compared with healthy controls (39.9 ± 13.1 vs. 33.6 ± 5.3, p = 0.019). Expressions of all other receptors were similar in BD and control group. Of particular interest, TLR2 expression on neutrophils was similar in both groups and, when stimulated with LTA, BD neutrophils showed chemotactic responses similar to the controls. Neutrophils exhibited increased chemotaxis only when incubated with BD plasma. Serum sCD14 concentration was higher in BD patients than in controls (1,920.8 ± 563.6 vs. 1,623.2 ± 391.3 ng/ml, p = 0.008), and it was positively correlated with both CD14 expression on circulating monocytes membrane (p = 0.035) and BDCAF scores (p = 0.025). In conclusion, isolated BD neutrophils do not overexpress TLR2 neither overreact to LTA. However, because TLR2 expression was higher on BD monocytes, sCD14 from monocyte origin correlated with disease activity and neutrophil hyperchemotaxis occurred on strict dependence of plasmatic soluble factors, we suggest a possible role for bacterial stimulation of monocytes via TLR2 producing neutrophil-stimulating pro-inflammatory factors in BD.

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Acknowledgements

We are grateful to Maria Aurora Gomes da Silva and Maria de Fátima de Almeida for their contributions to our laboratory chemotaxis experiments and to Rogério Ruscitto do Prado for statistical assistance. Discussions with many colleagues were important during this study, but we are particularly grateful to Dr. Roger Chammas, Ph.D. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 2007/52448-4].

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  1. Rheumatology Division, University of São Paulo (USP), São Paulo, Brazil

    Fabricio Souza Neves, Solange Carrasco, Cláudia Goldenstein-Schainberg, Célio Roberto Gonçalves & Suzana Beatriz Veríssimo de Mello

  2. Disciplina de Reumatologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 3º andar, sala 3133, Pacaembu, São Paulo, 01246-903, SP, Brazil

    Fabricio Souza Neves

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  1. Fabricio Souza Neves
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Correspondence to Fabricio Souza Neves.

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Neves, F.S., Carrasco, S., Goldenstein-Schainberg, C. et al. Neutrophil hyperchemotaxis in Behçet’s disease: a possible role for monocytes orchestrating bacterial-induced innate immune responses. Clin Rheumatol 28, 1403–1410 (2009). https://doi.org/10.1007/s10067-009-1261-5

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