RESUMEN
Syphilis caused by Treponema pallidum (T. pallidum) infection is accompanied by inflammatory injury of tissue, and has a worldwide distribution and increasing incidence over the past decade. Tp17 has been reported to be a strong membrane immunogen, and was initially observed to play a role in inflammation during syphilis, reacting intensely with human syphilitic sera. We therefore used recombinant Tp17 (rTp17) as a stimulator in our study. Increasing evidence has demonstrated that microRNA (miRNA)-containing exosomes have emerged as a potential effective therapeutic target for many diseases. However, the biological functions and molecular mechanisms of miR-216a-5p in syphilis pathogenesis remain unknown. Our study first identified dramatically decreased miR-216a-5p in plasma of syphilis patients compared with the healthy control, which was negatively correlated with the expression of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Moreover, endothelial cells treated with miR-216a-5p-containing exosomes significantly attenuated the rTp17-induced inflammatory response. More importantly, we identified that miR-216a-5p could bind to the 3'-untranslated region (UTR) of Toll-like receptor (TLR) 4 (TLR4), and overexpression of TLR4 largely rescued the miR-216a-5p-mediated suppression of rTp17-induced inflammatory cytokine production and the TLR4-MYD88 signaling pathway. Thus, our results reveal a novel role of miR-216a-5p-containing exosomes in endothelial cells, implying a potential therapeutic target for inflammation in syphilis patients.
Asunto(s)
Proteínas Bacterianas/inmunología , Exosomas/inmunología , MicroARNs/inmunología , Transducción de Señal/inmunología , Sífilis/inmunología , Receptor Toll-Like 4/inmunología , Treponema pallidum/inmunología , Proteínas Bacterianas/genética , Citocinas/inmunología , Exosomas/patología , Femenino , Células Endoteliales de la Vena Umbilical Humana/inmunología , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Masculino , Factor 88 de Diferenciación Mieloide/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Sífilis/patología , Treponema pallidum/genéticaAsunto(s)
Interferón-alfa/administración & dosificación , Papulosis Linfomatoide/tratamiento farmacológico , Mecloretamina/administración & dosificación , Femenino , Humanos , Interferón alfa-2 , Papulosis Linfomatoide/patología , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , SolucionesRESUMEN
BACKGROUND: Treponema pallidum (T. pallidum) subsp. pallidum is the causative agent of syphilis. Analysis of recombinant antigens of T. pallidum led to the identification of potential candidate antigens for vaccine development and syphilis serodiagnosis. Tp0965 was predicted to be a membrane fusion protein and was found to be reactive with infected human sera in previous studies, but the results were controversial. In this research, the antigenicity and immunoreactivity of recombinant protein Tp0965 were assessed. METHODS: T. pallidum subsp. pallidum (Nichols strain) was propagated and isolated and the genomic DNA was extracted. The Tp0965 gene was amplified by polymerase chain reaction (PCR). Then the recombinant protein Tp0965 was expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid (Ni-NTA) purification system. The reactivities of protein Tp0965 were examined by immunoblot analysis and indirect enzyme-linked immunosorbent assay. The antisera against protein Tp0965 were obtained by immune rabbits and the immunogenicity of antisera were detected by indirect enzyme-linked immunosorbent assay. RESULTS: Recombinant protein Tp0965 was expressed successfully in vitro. Immunoblot assay showed that the recombinant protein Tp0965 could be recognized by human syphilitic sera of all stages. Indirect enzyme-linked immunosorbent assay showed there were only 4 of 74 human syphilitic sera that failed to show reactivity to recombinant antigen Tp0965, and lack of reactivity of Tp0965 to all 28 uninfected sera. A low titer of antiserum against Tp0965 in immune rabbits could be detected after the third time of immunization. CONCLUSIONS: The recombinant antigen Tp0965 shows excellent sensitivity for the reactivity with sera from syphilitic individuals at all stages. The results also demonstrate a potential application for the serodiagnosis of syphilis.
Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Proteínas de la Membrana/inmunología , Treponema pallidum/inmunología , Treponema pallidum/metabolismo , Animales , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Ensayo de Inmunoadsorción Enzimática , Humanos , Proteínas de la Membrana/genética , Reacción en Cadena de la Polimerasa , Conejos , Sífilis/inmunología , Sífilis/microbiologíaRESUMEN
Children may acquire syphilis as a consequence of nonsexual close contact if family members or caregivers are infected by active syphilis. We described 3 cases of acquired secondary syphilis in Chinese preschool children who contracted the disease from their caregivers to draw attention to the potential for syphilis patients to transmit Treponema pallidum to the children they are caretakers for.