transforming-growth-factor-beta and Syphilis

Recent studies have shown that several long noncoding RNAs (lncRNAs) are involved in regulating the immune response to cope with pathogenic invasion. To date, the roles of lncRNAs in the CD4+ T cell response to

Topics: Adult; Aged; Bacteria; CD4-Positive T-Lymphocytes; China; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Humans; Male; Microarray Analysis; Middle Aged; Neurosyphilis; RNA, Long Noncoding; RNA, Messenger; Syphilis; Transforming Growth Factor beta; Treponema pallidum; Young Adult

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.

Topics: Adult; Antigens, Helminth; Cell Differentiation; Cells, Cultured; Down-Regulation; Female; Humans; Inflammasomes; Inflammation Mediators; Male; Middle Aged; Monocytes; Syphilis; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Treponema pallidum; Virulence Factors

Using a semi-quantitative multiplex reverse transcription-polymerase chain reaction assay, we examined cytokine mRNA expression for interleukin-1alpha (IL-1alpha), IL-2, IL-10, IL-12p40, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) in skin samples obtained from C4-deficient (C4D) guinea-pigs inoculated intradermally with virulent Treponema pallidum (VTP). Controls included unmanipulated animals, guinea-pigs injected with T. pallidum-free rabbit inflammatory testicular fluid (ITF) alone, or mixed with heat-killed organisms (HKTP). The expression of IL-1alpha, IL-12p40, and TNF-alpha mRNA [T helper type 1 (Th1)] remained within the normal range in both infected and control animals throughout the experimental period. However, a significant increase (P<0.05) in IL-10 mRNA (Th2) was found exclusively in the VTP-inoculated animals from 3 to 30 days post-infection. Another unique characteristic of the inflammatory response in infected guinea-pigs was the appearance, between 11 and 30 days post-inoculation, of a substantial number of eosinophils in addition to infiltrating mononuclear cells. The results showed a local Th2 response which is consistent with an inadequate immune response. This is reflected by the lengthy and incomplete clearance of the pathogen from the local site of entry and the chronic infection of distant organs.

Topics: Animals; Cytokines; Eosinophilia; Gene Expression; Guinea Pigs; Interleukin-1; Interleukin-10; Interleukin-12; Interleukin-2; Male; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Skin; Syphilis; Transforming Growth Factor beta; Treponema pallidum; Tumor Necrosis Factor-alpha