We developed a new Boson chemiluminescence immunoassay (CIA) and evaluated its application with cross-sectional analyses. Our results indicated that the Boson CIA demonstrated strong discriminatory power in diagnosing syphilis and that it can be used as a first-line screening test for syphilis serodiagnosis using the European Centre for Disease Prevention and Control algorithm or as a confirmatory test when combined with a patient's clinical history.
Abstract Background Elucidating the mechanism of the macrophage phagocytic response will improve our knowledge of host defence against Treponema pallidum . Objective To explore whether autophagy promotes T. pallidum phagocytosis and clearance via the NLRP3 inflammasome in macrophages. Methods The interactions between autophagy and phagocytosis and the role of NLRP3 in these processes in T. pallidum ‐treated macrophages were investigated through experiments using human monocytic cell line (THP‐1)‐derived macrophages. Treponema pallidum clearance after phagocytosis was evaluated by inoculating rabbits with macrophage–treponeme mixtures. Results Activation of autophagy and phagocytosis in T. pallidum‐ treated macrophages occurred in a dose‐ and time‐dependent manner. The percentage of spirochete‐positive macrophages (22.34% vs. 70.93%, P < 0.001) and spirochete internalization (MFI: 9.62 vs. 20.33, P < 0.001) were notably reduced by silencing Beclin1 . Inoculation of macrophage–treponeme mixtures into rabbits showed a 3.00‐day delay in lesion development (17.55 ± 3.73 vs. 14.55 ± 1.99 days) and decreased lesion numbers [11 (36.7%) vs. 20 (66.7%) of 30; χ 2 = 5.406, P = 0.020] in the control compared with the si‐ Beclin1 group. Furthermore, silencing NLRP3 decreased the mRNA and protein levels of Beclin‐1 and LC3B [mRNA: 49.86% and 43.02%; protein: 22.31% and 24.24%, respectively, differing significantly from the control group ( P < 0.001)] and reduced the percentage of spirochete‐positive macrophages (30.29% vs. 70.53%, P < 0.001) and spirochete internalization (MFI: 9.82 vs. 19.33, P < 0.001). Conclusion Treponema pallidum induces autophagy in macrophages to promote phagocytosis and clearance. The NLRP3 inflammasome modulates autophagy and phagocytosis in vitro . These data may be useful for understanding the host–pathogen relationship and establish the groundwork for strategies to combat syphilis.
Teleost type I interferons (IFNs) are categorized into group I and II subgroups that bind to distinct receptors to activate antiviral responses. However, the interaction between ifn ligands and receptors has not fully been understood. In this study, the crystal structure of grass carp [ Ctenopharyngodon idella ( Ci )] IFNa has been solved at 1.58Å and consists of six helices. The Ci IFNa displays a typical structure of type I IFNs with a straight helix F and lacks a helix element in the AB loop. Superposition modeling identified several key residues involved in the interaction with receptors. It was found that Ci IFNa bound to cytokine receptor family B (CRFB) 1, CRFB2, and CRFB5, and the three receptors could form heterodimeric receptor complexes. Furthermore, mutation of Leu27, Glu103, Lys117, and His165 markedly decreased the phosphorylation of signal transducer and activator of transcription (STAT) 1a induced by Ci IFNa in the Epithelioma papulosum cyprini (EPC) cells, and Glu103 was shown to be required for the Ci IFNa-activated antiviral activity. Interestingly, wild-type and mutant Ci IFNa proteins did not alter the phosphorylation levels of STAT1b. Our results demonstrate that fish type I IFNs, although structurally conserved, interact with the receptors in a manner that may differ from mammalian homologs.
The origin of nontreponemal antibodies during syphilis infection is hotly debated. Here, we analyzed the immune response in rabbits immunized with various antigens. Inactivated treponemes elicited the production of low-titer nontreponemal antibodies in some rabbits. Cardiolipin combined with bovine serum albumin also induced anticardiolipin antibody production. These findings indicate that Treponema pallidum contained a cardiolipin antigen with weak immunogenicity. However, active T. pallidum induced higher nontreponemal antibody production with strong immunogenicity at an earlier time point, and the antibody titer was consecutive, suggesting the high nontreponemal antibody titer resulted from the combined effects of both the T. pallidum cardiolipin antigen and the damaged host-cell cardiolipin antigen during syphilis infection, the latter of which plays a major role in the induction of nontreponemal antibody production. Our study provides direct animal evidence of the origin of nontreponemal antibodies during T. pallidum infection.
In order to study the deterioration law of anti-seepage curtain in high-pressure waterway of pumped storage power station, a mathematical model of multi-field coupling of anti-seepage curtain is established based on the principles of fluid dynamics, solute migration and chemical kinetics. The model is solved by finite element method and verified by engineering data. The research results show that the internal calcium of the anti-seepage curtain of high-pressure waterway is continuously dissolved and separated under the penetration and corrosion action of high water head for 30 years. In the deepest part of the anti-seepage curtain, 17.76% of solid calcium was dissolved and lost, its porosity increased by 29.38% compared with the initial porosity, the permeability coefficient increased by 2.49 times, and the impermeability and durability continued to decline. The seepage-corrosion damage of the high-pressure water channel anti-seepage curtain has the characteristics of temporal and spatial variation. The corrosion area of the contact part between the middle of the anti-seepage curtain and the high-pressure bifurcated pipe is the largest, while the top and bottom dissolution are mainly encircling dissolution, and its dissolution area is the second. The research results can provide a scientific basis for various preventive measures and control strategies to limit the deterioration of the anti-seepage performance of the high-pressure water channel anti-seepage curtain.
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