ZFIN ID: ZDB-PUB-160106-9
Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway
Pozzobon, T., Facchinello, N., Bossi, F., Capitani, N., Benagiano, M., Di Benedetto, G., Zennaro, C., West, N., Codolo, G., Bernardini, M., Baldari, C.T., D'Elios, M.M., Pellegrini, L., Argenton, F., de Bernard, M.
Date: 2016
Source: Scientific Reports   6: 18785 (Journal)
Registered Authors: Argenton, Francesco, Facchinello, Nicola
Keywords: Bacterial pathogenesis, Infection
MeSH Terms:
  • Animals
  • Antigens, Bacterial/immunology*
  • Antigens, Helminth/immunology*
  • Antigens, Helminth/metabolism
  • Cell Movement
  • Cell Proliferation
  • Chemokine CCL20/metabolism
  • Cyclic AMP Response Element-Binding Protein/metabolism
  • Endothelial Cells/metabolism
  • Gene Expression
  • Humans
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Interleukin-8/genetics
  • Interleukin-8/metabolism*
  • Monocytes/immunology
  • Monocytes/metabolism
  • NF-kappa B/metabolism
  • Neovascularization, Pathologic*
  • Recombinant Proteins/immunology
  • Recombinant Proteins/metabolism
  • Signal Transduction*
  • Syphilis/genetics
  • Syphilis/immunology
  • Syphilis/metabolism
  • T-Lymphocytes/immunology
  • T-Lymphocytes/metabolism
  • Treponema pallidum/immunology*
  • Zebrafish
PubMed: 26728351 Full text @ Sci. Rep.
Over 10 million people every year become infected by Treponema pallidum and develop syphilis, a disease with broad symptomatology that, due to the difficulty to eradicate the pathogen from the highly vascularized secondary sites of infection, is still treated with injections of penicillin. Unlike most other bacterial pathogens, T. pallidum infection produces indeed a strong angiogenic response whose mechanism of activation, however, remains unknown. Here, we report that one of the major antigen of T. pallidum, the TpF1 protein, has growth factor-like activity on primary cultures of human endothelial cells and activates specific T cells able to promote tissue factor production. The growth factor-like activity is mediated by the secretion of IL-8 but not of VEGF, two known angiogenic factors. The pathogen's factor signals IL-8 secretion through the activation of the CREB/NF-κB signalling pathway. These findings are recapitulated in an animal model, zebrafish, where we observed that TpF1 injection stimulates angiogenesis and IL-8, but not VEGF, secretion. This study suggests that the angiogenic response observed during secondary syphilis is triggered by TpF1 and that pharmacological therapies directed to inhibit IL-8 response in patients should be explored to treat this disease.