title: TpF1 from Treponema pallidum activates inflammasome and promotes the development of regulatory T cells.
abstract: Human syphilis is a multistage disease, with diverse and wide-ranging manifestations caused by Treponema pallidum. Despite the fact that a cell-mediated immune response takes part in the course of syphilis, T. pallidum often manages to evade host immunity and, in untreated individuals, may trigger chronic infection. With this study, we demonstrate for the first time, to our knowledge, that Treponema pallidum induces a regulatory T (Treg) response in patients with secondary syphilis and we found that the miniferritin TpF1, produced by the bacterium, is able to expand this response and promote the production of TGF-β. Accordingly, TpF1 stimulates monocytes to release IL-10 and TGF-β, the key cytokines in driving Treg cell differentiation. Interestingly, we also found that TpF1 stimulates monocytes to synthesize and release several proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, the latter following the activation of the multiprotein complex inflammasome. Collectively, these data strongly support a central role for TpF1 both in the inflammation process, which occurs in particular during the early stage of syphilis, and in the long-term persistence of the spirochete within the host by promoting Treg response and TGF-β production.
authors.affiliation: Venetian Institute of Molecular Medicine, Padua 35121, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Babolin
authors.forename: Amedeo
authors.initials: A
authors.lastname: Amedei
authors.forename: Dzintars
authors.initials: D
authors.lastname: Ozolins
authors.forename: Aija
authors.initials: A
authors.lastname: Zilevica
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D000328:Adult; D000947:Antigens, Helminth / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism* / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013587:Syphilis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism; D014210:Treponema pallidum / Q000254:growth & development / Q000276:immunology*; D037521:Virulence Factors / Q000096:biosynthesis / Q000502:physiology
chemical_list: D000947:Antigens, Helminth; D058847:Inflammasomes; D018836:Inflammation Mediators; C510510:TpF1 protein, Treponema pallidum; D016212:Transforming Growth Factor beta; D037521:Virulence Factors