Chlamydia trachomatis Plasmid Protein pORF5 Up-Regulates ZFAS1 to Promote Host Cell Survival via MAPK/p38 Pathway

Wen, Yang; Chen, Hongliang; Luo, Feilong; Zhao, Lanhua; Shu, Mingyi; Su, Shengmei; Zhao, Yuqi; Huang, Qiulin; Li, Zhongyu

doi:10.3389/fmicb.2020.593295

Cited by 13 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, there is no clinical vaccine for humans (20). Pgp3 is an important virulence protein encoded by the cryptic plasmid (21)(22)(23)(24). Our previous studies confirmed that Pgp3 was a conformationdependent immunodominant antigen, which was an expected vaccine candidate (25).…”

Section: Introductionmentioning

confidence: 84%

Preparation of graphene oxide–stabilized Pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against Chlamydia Trachomatis infection

et al. 2023

Self Cite

View full text Add to dashboard Cite

BackgroundTraditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and therefore has potential to be used as a surfactant substitute to stabilize Pickering emulsions.MethodsIn this study, GO–stabilized Pickering emulsion (GPE) was prepared and used as an adjuvant to facilitate an enhanced immune response to the Chlamydia trachomatis (Ct) Pgp3 recombinant vaccine. Firstly, GPE was prepared by optimizing the sonication conditions, pH, salinity, GO concentration, and water/oil ratio. GPE with small-size droplets was characterized and chosen as the candidate. Subsequently, controlled-release antigen delivery by GPE was explored. Cellular uptake behaviors, M1 polarization, and cytokine stimulation by GPE + Pgp3 was considered in terms of the production of macrophages. Finally, GPE’s adjuvant effect was evaluated by vaccination with Pgp3 recombinant in BALB/c mouse models.ResultsGPE with the smallest droplet sizes was prepared by sonication under 163 W for 2 min at 1 mg/mL GO in natural salinity with a pH of 2 when the water/oil ratio was 10:1 (w/w). The optimized average GPE droplet size was 1.8 μm and the zeta potential was –25.0 ± 1.3 mv. GPE delivered antigens by adsorption onto the droplet surface, demonstrating the controlled release of antigens both in vitro and in vivo. In addition, GPE promoted antigen uptake, which stimulated proinflammatory tumor necrosis factor alpha (TNF-α), enhancing the M1 polarization of macrophages in vitro. Macrophage recruitment was also significantly promoted by GPE at the injection site. In the GPE + Pgp3 treatment group, higher levels of immunoglobin (IgG), immunoglobin G1 (IgG1), immunoglobin G2a (IgG2a) sera, and immunoglobin A (IgA) were detected in vaginal fluid, and higher levels of IFN-γ and IL-2 secretion were stimulated, than in the Pgp3 group, showing a significant type 1 T helper (Th1)-type cellular immune response. Chlamydia muridarum challenging showed that GPE enhanced Pgp3’s immunoprotection through its advanced clearance of bacterial burden and alleviation of chronic pathological damage in the genital tract.ConclusionThis study enabled the rational design of small-size GPE, shedding light on antigen adsorption and control release, macrophage uptake, polarization and recruitment, which enhanced augmented humoral and cellular immunity and ameliorated chlamydial-induced tissue damage in the genital tract.

show abstract

Section: Introductionmentioning

confidence: 84%

Preparation of graphene oxide–stabilized Pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against Chlamydia Trachomatis infection

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…It was predicted to regulate MAPK pathways and its silencing led to decrease in Chlamydia plasmid protein pORF5-mediated-apoptosis and Ct virulence (Figure 4C). The study concluded pORF5 crucial role in activation of lncRNA ZFAS1, and ZFAS1 mediated induction of MAPK/p38 pathway to inhibit host cell apoptosis (Wen et al, 2020a).…”

Section: Chlamydia Trachomatismentioning

confidence: 89%

The emerging roles of long non-coding RNA in host immune response and intracellular bacterial infections

Arunima

Schaik

Samuel

2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The long non-coding RNAs (lncRNAs) are evolutionarily conserved classes of non-coding regulatory transcripts of > 200 nucleotides in length. They modulate several transcriptional and post-transcriptional events in the organism. Depending on their cellular localization and interactions, they regulate chromatin function and assembly; and alter the stability and translation of cytoplasmic mRNAs. Although their proposed range of functionality remains controversial, there is increasing research evidence that lncRNAs play a regulatory role in the activation, differentiation and development of immune signaling cascades; microbiome development; and in diseases such as neuronal and cardiovascular disorders; cancer; and pathogenic infections. This review discusses the functional roles of different lncRNAs in regulation of host immune responses, signaling pathways during host-microbe interaction and infection caused by obligate intracellular bacterial pathogens. The study of lncRNAs is assuming significance as it could be exploited for development of alternative therapeutic strategies for the treatment of severe and chronic pathogenic infections caused by Mycobacterium, Chlamydia and Rickettsia infections, as well as commensal colonization. Finally, this review summarizes the translational potential of lncRNA research in development of diagnostic and prognostic tools for human diseases.

show abstract

“…Overall, there was acceptable biosafety with respect to CSPE and IL-12 as C. trachomatis vaccine adjuvant candidates. (53)(54)(55)(56), which was essential for the pathogenesis of C. trachomatis. Importantly, Pgp3 was regarded as a promising antigen for subunit vaccine candidates due to existing immunogenicity (17).…”

Section: Biocompatibility Assaysmentioning

confidence: 99%

Chitosan particle stabilized Pickering emulsion/interleukin-12 adjuvant system for Pgp3 subunit vaccine elicits immune protection against genital chlamydial infection in mice

et al. 2022

Self Cite

View full text Add to dashboard Cite

Considering the shortcomings in current chlamydia infection control strategies, a major challenge in curtailing infection is the implementation of an effective vaccine. The immune response induced by C. trachomatis plasmid encoded Pgp3 was insufficient against C. trachomatis infection, which requires adjuvant applications to achieve the robust immune response induced by Pgp3. There is increasing promising in developing adjuvant systems relying on the delivery potential of Pickering emulsions and the immunomodulatory effects of interleukin (IL)-12. Here, owing to the polycationic nature, chitosan particles tended to absorb on the oil/water interphase to prepare the optimized chitosan particle-stabilized Pickering emulsion (CSPE), which was designed as a delivery system for Pgp3 protein and IL-12. Our results showed that the average droplets size of CSPE was 789.47 ± 44.26 nm after a series of optimizations and about 90% antigens may be absorbed by CSPE owing to the positively charged surface (33.2 ± 3mV), and CSPE promoted FITC-BSA proteins uptake by macrophages. Furthermore, as demonstrated by Pgp3-specific antibody production and cytokine secretion, CSPE/IL-12 system enhanced significantly higher levels of Pgp3-specific IgG, IgG1, IgG2a, sIgA and significant cytokines secretion of IFN-γ, IL-2, TNF-α, IL-4. Similarly, vaginal chlamydial shedding and hydrosalpinx pathologies were markedly reduced in mice immunized with Pgp3/CSPE/IL-12. Collectively, vaccination with Pgp3/CSPE/IL-12 regimen elicited robust cellular and humoral immune response in mice resulting in an obvious reduction of live chlamydia load in the vaginal and inflammatory pathologies in the oviduct, which further propells the development of vaccines against C. trachomatis infection.

show abstract

Chlamydia trachomatis Plasmid Protein pORF5 Up-Regulates ZFAS1 to Promote Host Cell Survival via MAPK/p38 Pathway

Cited by 13 publications

References 35 publications

Preparation of graphene oxide–stabilized Pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against Chlamydia Trachomatis infection

Preparation of graphene oxide–stabilized Pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against Chlamydia Trachomatis infection

The emerging roles of long non-coding RNA in host immune response and intracellular bacterial infections

Chitosan particle stabilized Pickering emulsion/interleukin-12 adjuvant system for Pgp3 subunit vaccine elicits immune protection against genital chlamydial infection in mice

Contact Info

Product

Resources

About