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  • Aleem, Muhammad Tahir  (13)
  • Li, Xiangrui  (13)
  • 1
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    Molecular Docking and In Silico Simulation of Trichinella spiralis Membrane-Associated Progesterone Receptor Component 2 (Ts-MAPRC2) and Its Interaction with Human PGRMC1
    Hindawi Limited ; 2022
    In:  BioMed Research International Vol. 2022 ( 2022-6-20), p. 1-10
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2022 ( 2022-6-20), p. 1-10
    Abstract: Background. Trichinellosis is a foodborne zoonotic disease caused by Trichinella spp., including Trichinella spiralis. This parasitic disease ranks as seven of the most infectious in the world. In this context, it is important to develop a vaccine that can combat Trichinellosis, especially for humans and pigs. This would be an important step in preventing transmission. In this study, we focus on homology modelling, binding site prediction, molecular modelling, and simulation techniques used to explore the association between Trichinella spiralis membrane-associated progesterone receptor component 2 (Ts-MAPRC2) and the human PGRMC1 protein. It was found that the progesterone receptor component 2 of T. spiralis has 44.54% sequence identity with human PGRMC1 (PDB ID: 4X8Y). Binding sites predicted for human PGRMC1 are GLU 7, PHE 8, PHE 10, PHE 18, LEU 27, ASP 36, and VAL 104. Molecular docking has six clusters based on Z scores. They range from -1.5 to 1.8. It was found that the progesterone receptor component 2 of T. spiralis has 44.54% sequence identity with human PGRMC1. During simulation, the average RMSD was 2.44 ± 0.20   Å , which indicated the overall stability of the protein. Based on docking studies and computational simulations, we hypothesized that the interaction of the proteins Trichinella spiralis membrane-associated progesterone receptor component 2 and human PGRMC1 formed stable complexes. The discovery of Ts-MAPRC2 may pave the way for the development of drugs and vaccines to treat Trichinellosis.
    Type of Medium: Online Resource
    ISSN: 2314-6141 , 2314-6133
    URL: Article
    DOI: 10.1155/2022/7414198
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2698540-8
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  • 2
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-4)
    Abstract: Trehalose phosphate synthase (TPS), a key enzyme in trehalose synthesis, is not present in mammals but critical to the viability of a wide range of lower organisms. However, almost nothing is known about the function of Hc-TPS (GT1-TPS structural domain protein from Haemonchus contortus ). In this study, Hc-TPS gene was cloned and the recombinant protein (rHc-TPS) was expressed and purified. The quantitative real-time PCR (qPCR) results showed that Hc-TPS was transcribed at different stages of H. contortus , with higher levels of transcription at the molting and embryo stages. Immunofluorescence analysis showed that Hc-TPS was widely distributed in adults, but the expression was mainly localized on the mucosal surface of the intestine as well as in the embryos of female worms. The impacts of rHc-TPS on peripheral blood mononuclear cell (PBMC) proliferation, nitric oxide (NO) generation, transcriptional expression of cytokines, and related pathways were examined by co-incubating rHc-TPS with goat PBMCs. The results showed that rHc-TPS significantly inhibited PBMC proliferation and NO secretion in a dose-dependent manner. We also found that rHc-TPS activated the interleukin (IL)-10/signal transducer and activator of transcription 3/suppressor of cytokine signaling 3 (IL-10/STAT3/SOCS3) axis and significantly promoted SOCS3 expression, while inhibiting interferon-gamma (INF-γ), IL-4, IL-9, and IL-2 pathways. Our findings may contribute to understanding the immune evasion mechanism for the parasite during host–parasite interactions and also help to provide ideas for discovering new drug targets.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.787091
    DOI: 10.3389/fimmu.2021.787091.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
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    With Chitosan and PLGA as the Delivery Vehicle, Toxoplasma gondii Oxidoreductase-Based DNA Vaccines Decrease Parasite Burdens in Mice
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-8-27)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-8-27)
    Abstract: Toxoplasma gondii ( T. gondii ) is an intracellular parasitic protozoan that can cause serious public health problems. However, there is no effectively preventive or therapeutic strategy available for human and animals. In the present study, we developed a DNA vaccine encoding T. gondii oxidoreductase from short-chain dehydrogenase/reductase family (TgSDRO-pVAX1) and then entrapped in chitosan and poly lactic-co-glycolic acid (PLGA) to improve the efficacy. When encapsulated in chitosan (TgSDRO-pVAX1/CS nanospheres) and PLGA (TgSDRO-pVAX1/PLGA nanospheres), adequate plasmids were loaded and released stably. Before animal immunizations, the DNA vaccine was transfected into HEK 293-T cells and examined by western blotting and laser confocal microscopy. Th1/Th2 cellular and humoral immunity was induced in immunized mice, accompanied by modulated secretion of antibodies and cytokines, promoted the maturation and MHC expression of dendritic cells, and enhanced the percentages of CD4 + and CD8 + T lymphocytes. Immunization with TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres conferred significant immunity with lower parasite burden in the mice model of acute toxoplasmosis. Furthermore, our results also lent credit to the idea that TgSDRO-pVAX1/CS and TgSDRO-pVAX1/PLGA nanospheres are substitutes for each other. In general, the current study proposed that TgSDRO-pVAX1 with chitosan or PLGA as the delivery vehicle is a promising vaccine candidate against acute toxoplasmosis.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.726615
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Immunodiagnostic potential of recombinant tropomyosin during prepatent Haemonchus contortus infection in goat
    Elsevier BV ; 2020
    In:  Research in Veterinary Science Vol. 128 ( 2020-02), p. 197-204
    Details
    In: Research in Veterinary Science, Elsevier BV, Vol. 128 ( 2020-02), p. 197-204
    Type of Medium: Online Resource
    ISSN: 0034-5288
    URL: Article
    DOI: 10.1016/j.rvsc.2019.11.013
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2002535-X
    SSG: 22
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  • 5
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    Nano DNA Vaccine Encoding Toxoplasma gondii Histone Deacetylase SIR2 Enhanced Protective Immunity in Mice
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 10 ( 2021-09-29), p. 1582-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 10 ( 2021-09-29), p. 1582-
    Abstract: The pathogen of toxoplasmosis, Toxoplasma gondii (T. gondii), is a zoonotic protozoon that can affect the health of warm-blooded animals including humans. Up to now, an effective vaccine with completely protection is still inaccessible. In this study, the DNA vaccine encoding T. gondii histone deacetylase SIR2 (pVAX1-SIR2) was constructed. To enhance the efficacy, chitosan and poly (d, l-lactic-co-glycolic)-acid (PLGA) were employed to design nanospheres loaded with the DNA vaccine, denoted as pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres. The pVAX1-SIR2 plasmids were transfected into HEK 293-T cells, and the expression was evaluated by a laser scanning confocal microscopy. Then, the immune protections of pVAX1-SIR2 plasmid, pVAX1-SIR2/CS nanospheres, and pVAX1-SIR2/PLGA nanospheres were evaluated in a laboratory animal model. The in vivo findings indicated that pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres could generate a mixed Th1/Th2 immune response, as indicated by the regulated production of antibodies and cytokines, the enhanced maturation and major histocompatibility complex (MHC) expression of dendritic cells (DCs), the induced splenocyte proliferation, and the increased percentages of CD4+ and CD8+ T lymphocytes. Furthermore, this enhanced immunity could obviously reduce the parasite burden in immunized animals through a lethal dose of T. gondii RH strain challenge. All these results propose that pVAX1-SIR2 plasmids entrapped in chitosan or PLGA nanospheres could be the promising vaccines against acute T. gondii infections and deserve further investigations.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13101582
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 6
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    Toxoplasma gondii Proteasome Subunit Alpha Type 1 with Chitosan: A Promising Alternative to Traditional Adjuvant
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 5 ( 2021-05-19), p. 752-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 5 ( 2021-05-19), p. 752-
    Abstract: As an important zoonotic protozoan, Toxoplasma gondii (T. gondii) has spread around the world, leading to infections in one-third of the population. There is still no effective vaccine or medicine against T. gondii, and recombinant antigens entrapped within nanospheres have benefits over traditional vaccines. In the present study, we first expressed and purified T. gondii proteasome subunit alpha type 1 (TgPSA1), then encapsulated the recombinant TgPSA1 (rTgPSA1) in chitosan nanospheres (CS nanospheres, rTgPSA1/CS nanospheres) and incomplete Freund’s adjuvant (IFA, rTgPSA1/IFA emulsion). Antigens entrapped in CS nanospheres reached an encapsulation efficiency of 67.39%, and rTgPSA1/CS nanospheres showed a more stable release profile compared to rTgPSA1/IFA emulsion in vitro. In vivo, Th1-biased cellular and humoral immune responses were induced in mice and chickens immunized with rTgPSA1/CS nanospheres and rTgPSA1/IFA emulsion, accompanied by promoted production of antibodies, IFN-γ, IL-4, and IL-17, and modulated production of IL-10. Immunization with rTgPSA1/CS nanospheres and rTgPSA1/IFA emulsion conferred significant protection, with prolonged survival time in mice and significantly decreased parasite burden in chickens. Furthermore, our results also indicate that rTgPSA1/CS nanospheres could be used as a substitute for rTgPSA1/IFA emulsion, with the optimal administration route being intramuscular in mass vaccination. Collectively, the results of this study indicate that rTgPSA1/CS nanospheres represent a promising vaccine to protect animals against acute toxoplasmosis.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13050752
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 7
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    Inhibition of Trichinella spiralis Membrane-Associated Progesterone Receptor (MAPR) Results in a Reduction in Worm Burden
    MDPI AG ; 2023
    In:  Vaccines Vol. 11, No. 9 ( 2023-08-31), p. 1437-
    Details
    In: Vaccines, MDPI AG, Vol. 11, No. 9 ( 2023-08-31), p. 1437-
    Abstract: Trichinella spiralis (T. spiralis), a nematode parasite, is the major cause of Trichinellosis, a zoonotic disease. A key role of MAPR in the reproductive system is to maintain pregnancy. Previous studies found that antihormone drug design and vaccine therapy of recombinant protein (rTs-MAPRC2) control T. spiralis infection. The current study investigates the inhibitory effects of different ratios of antibodies against Ts-MAPRC2 on the development of muscle larvae (ML) and newborn larvae (NBL). First, we performed indirect immunofluorescence assays and examined the effects of rTs-MAPRC2-Ab on ML and NBL in vitro as well as in vivo. Afterward, siRNA-Ts-MAPRC2 was transfected into T. spiralis muscle larvae. Following that, Ts-MAPRC2 protein was detected by Western Blotting, and mRNA levels were determined by qPCR. We also assessed whether siRNA-treated NBLs were infective by analyzing muscle larvae burden (MLs). Our results showed that rTs-MAPRC2-Ab greatly inhibited the activity of the Ts-MAPRC2 in ML and NBL of T. spiralis and rTs-MAPRC2-Ab reduced larval infectivity and survival in the host in a dose-dependent manner (1:50, 1:200, 1:800 dilutions). Furthermore, siRNA-Ts-MAPRC2 effectively silenced the Ts-MAPRC2 gene in muscle larvae (ML) in vitro, as well as in newborn larvae (NBL) of T. spiralis in vivo. In addition, siRNA-Ts-MAPRC2 (siRNA180, siRNA419, siRNA559) reduced host larval survival and infectivity significantly. This study, therefore, suggests that Ts-MAPRC2 might be a novel molecular target useful in the development of vaccines against T. spiralis infection.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines11091437
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2703319-3
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  • 8
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    Identification of excretory and secretory proteins from Haemonchus contortus inducing a Th9 immune response in goats
    Springer Science and Business Media LLC ; 2022
    In:  Veterinary Research Vol. 53, No. 1 ( 2022-12)
    Details
    In: Veterinary Research, Springer Science and Business Media LLC, Vol. 53, No. 1 ( 2022-12)
    Abstract: Th9 cells have been shown to play crucial roles in anti-parasite immunity, pathogenic microbe infection, and allergy. Previous studies have demonstrated that Haemonchus contortus excretory and secretory proteins (HcESPs) induce the proliferation of Th9 cells and alter the transcriptional level of IL-9 as well as its related pathways in the Th9 immune response after infection. However, the exact molecule(s) in HcESPs inducing the Th9 immune response is not yet known. In this study, flow cytometry, co-immunoprecipitation (Co-IP) and shotgun liquid chromatography tandem-mass spectrometry (LC–MS/MS) were used, and a total of 218 proteins from HcESPs that might interact with goat Th9 cells were identified. By in vitro culture of Th9 cells with HcESPs, 40 binding proteins were identified. In vivo, 38, 47, 42 and 142 binding proteins were identified at 7, 15, 35 and 50 days post-infection (dpi), respectively. Furthermore, 2 of the 218 HcESPs, named DNA/RNA helicase domain containing protein (HcDR) and GATA transcription factor (HcGATA), were confirmed to induce the proliferation of Th9 cells and promote the expression of IL-9 when incubated with goat peripheral blood mononuclear cells (PBMCs). This study represents a proteomics-guided investigation of the interactions between Th9 cells and HcESPs. It provides a new way to explore immunostimulatory antigens among HcESPs and identifies candidates for immune-mediated prevention of H. contortus infection.
    Type of Medium: Online Resource
    ISSN: 1297-9716
    URL: Article
    DOI: 10.1186/s13567-022-01055-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2012391-7
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  • 9
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-9-27)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-27)
    Abstract: Haemonchus contortus is an important parasitic nematode of ruminants. Previous studies showed that H. contortus escape the immunity through complex mechanisms, including releasing excretory/secretory proteins (ESPs) to modulate the host immune response. However, the detailed mechanism through which H. contortus excretory/secretory proteins (HcESPs) promote immune evasion remains unknown. In the present study, we demonstrated that HcESPs inhibit the adaptive immune response of goats including downregulation of immune cell antigen presentation, upregulation of immune checkpoint molecules, activation of the STAT3/PD-L1 pathway, and activation of immunosuppressive regulatory T (Treg) cells. Furthermore, HcESPs reversed the LPS-induced upregulation of pro-inflammatory mediators in PBMCs by inhibiting the TLR4/NF-κB/MAPKs/NLRP3 signaling pathway. Our study provides a better understanding of the evasion mechanisms for H. contortus , which could be helpful in providing an alternative way to prevent the infection of this parasite.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1013159
    DOI: 10.3389/fimmu.2022.1013159.s001
    DOI: 10.3389/fimmu.2022.1013159.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
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    Recombinant Toxoplasma gondii Ribosomal Protein P2 Modulates the Functions of Murine Macrophages In Vitro and Provides Immunity against Acute Toxoplasmosis In Vivo
    MDPI AG ; 2021
    In:  Vaccines Vol. 9, No. 4 ( 2021-04-07), p. 357-
    Details
    In: Vaccines, MDPI AG, Vol. 9, No. 4 ( 2021-04-07), p. 357-
    Abstract: Almost every warm-blooded animal can be an intermediate host for Toxoplasma gondii (T. gondii); there is still no efficient vaccine and medicine available for T. gondii infections. Detected on the surface of free tachyzoites of T. gondii, T. gondii ribosomal protein P2 (TgRPP2) has been identified as a target for protection against toxoplasmosis. In the present study, TgRPP2 was firstly expressed in a prokaryotic expression system, and the purified recombinant TgRPP2 (rTgRPP2) was characterized by its modulation effects on murine macrophages. Then, the purified rTgRPP2 was injected into mice to evaluate the immune protection of rTgRPP2. The results indicated that rTgRPP2 could bind to murine Ana-1 cells and showed good reactogenicity. After incubation with purified rTgRPP2, the proliferation, apoptosis, phagocytosis, nitric oxide (NO) production, and cytokines secreted by murine macrophages were modulated. Furthermore, the in vivo experiments indicated that animals immunized with rTgRPP2 could generate a significantly high level of antibodies, cytokines, and major histocompatibility complex (MHC) molecules, leading to a prolonged survival time. All of the results indicated that murine macrophages could be regulated by rTgRPP2 and are essential for the maintenance of tissue homeostasis. Immunization with rTgRPP2 triggered significant protection, with prolonged survival time in a mice model of acute toxoplasmosis. Our results lend credibility to the idea that rTgRPP2 could be a potential target for drug design and vaccine development.
    Type of Medium: Online Resource
    ISSN: 2076-393X
    URL: Article
    DOI: 10.3390/vaccines9040357
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2703319-3
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