title: Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway.
abstract: 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.
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pozzobon
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Facchinello
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Nagaja
authors.initials: N
authors.lastname: Capitani
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Benagiano
authors.affiliation: Institute of Neuroscience, Italian National Research Council (CNR), Padua, Italy.|Venetian Institute of Molecular Medicine, Padua, Italy.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Di Benedetto
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Nicole
authors.initials: N
authors.lastname: West
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Codolo
authors.affiliation: Department of Biology and Biotechnology, Sapienza University of Rome, Rome, Italy.
authors.forename: Marialina
authors.initials: M
authors.lastname: Bernardini
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Cosima Tatiana
authors.initials: CT
authors.lastname: Baldari
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec, Canada.
authors.forename: Luca
authors.initials: L
authors.lastname: Pellegrini
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Argenton
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000947:Antigens, Helminth / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D054418:Chemokine CCL20 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013587:Syphilis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014210:Treponema pallidum / Q000276:immunology*; D015027:Zebrafish
chemical_list: D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D054418:Chemokine CCL20; D017362:Cyclic AMP Response Element-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D011994:Recombinant Proteins; C510510:TpF1 protein, Treponema pallidum