trehalose-6-6--dibehenate and Tuberculosis

Topics: Adjuvants, Immunologic; Animals; Binding Sites; Cattle; Cell Line; Female; Humans; Lectins, C-Type; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Receptors, Immunologic; Structure-Activity Relationship; Trehalose; Tuberculosis; Tuberculosis Vaccines

Tuberculosis has been a major health problem worldwide for years; therefore, it is important to develop and produce an effective vaccine against this disease. In this study, the immunogenicity of Mycobacterium tuberculosis fusion protein (FP) encapsulated in liposomes containing DDA/TDB was evaluated. The FP was expressed in E. coli BL21 and encapsulated in liposomal formulations. Three weeks after the last subcutaneous immunization, IFN-γ, IL-4, IL-17, and IL-12 in spleen cell culture supernatants, and IgG2a, IgG1, and IgG2b titres in sera were measured. The greatest IFN-γ and IL-12 interleukin concentrations were observed in the DDA/TDB/CHOL liposomes containing the FP. Initial injection with BCG improved the efficacy of the DDA/TDB/CHOL/FP vaccine. The IgG2a/IgG1 ratio was also high in the DDA/TDB/CHOL/FP group; furthermore, the IgG2a/IgG1 ratio was increased in the BCG-primed, DDA/TDB/CHOL/FP-boosted group, indicating induction of a cellular immune response. Our study showed that the FP-containing DDA/TDB/CHOL liposomes induced a Th1 response. However, the groups that first received BCG and then DDA/TDB/CHOL/FP had the greatest Th1 response in terms of IFN-γ and IL-12 production of all the groups. This suggests that these formulations enhance the BCG vaccine's effectiveness.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; BCG Vaccine; Cytokines; Glycolipids; Liposomes; Mice; Quaternary Ammonium Compounds; Tuberculosis; Virulence Factors

Gut microbial components serve as ligand for various pattern recognition receptors (PRRs) present on immune cells and thereby regulates host immunity. Dendritic cells (DCs) are highly specialized innate cells involved in immune response to

Topics: Animals; Anti-Bacterial Agents; CD4-Positive T-Lymphocytes; Dendritic Cells; Dysbiosis; Gastrointestinal Microbiome; Glycolipids; Immunity, Innate; Lactobacillus; Lectins, C-Type; Lung; Macrophages; Membrane Proteins; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis; Receptors, Pattern Recognition; Tuberculosis

To investigate the effect of PKC δ gene on the anti-tuberculosis activity of macrophages and the mechanism.. Bone marrow cells of PKC δ knockout mice and wild-type mice were cultured and L929 cells were induced to differentiate into macrophages. Lipopolysaccharide (LPS) and trehalose 6,6'-dimycolate (TDM) were used to stimulate macrophages respectively. After 24 and 96 hours, cells and the supernatant were collected to evaluate the inflammatory cytokines produced by macrophages using ELISA method. Real-time PCR was performed to detect the expression of macrophage mRNA level and nitric oxide (NO) production of macrophages was measured by NO assay.. The results showed that, after TDB stimulation, IL-1β, IL-6, and other cytokines, as well as NO produced by macrophages of PKC δ knockout mice, were significantly decreased (p < 0.01) compared with the wild-type mice. In PKC δ knockout macrophages, the above protein-coding genes were also decreased significantly at the transcriptional level (p < 0.01).. PKC δ can enhance the anti-tuberculosis capacity of macrophages by inducing to the release of inflammatory factors by macrophages.

Topics: Animals; Cell Line; Disease Models, Animal; Glycolipids; Humans; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; Mice, Knockout; Mycobacterium tuberculosis; Primary Cell Culture; Protein Kinase C-delta; Tuberculosis

The adjuvanticity of liposomes can be directed through formulation to develop a safe yet potent vaccine candidate. With the addition of the cationic lipid dimethyldioctadecylammonium bromide (DDA) to stable neutral distearoylphosphatidylcholine (DSPC):cholesterol (Chol) liposomes, vesicle size reduces while protein entrapment increases. The addition of the immunomodulator, trehalose 6,6-dibehenate (TDB) to either the neutral or cationic liposomes did not affect the physiochemical characteristics of these liposome vesicles. However, the protective immune response, as indicated by the amount of IFN-γ production, increases considerably when TDB is present. High levels of IFN-γ were observed for cationic liposomes; however, there was a marked reduction in IFN-γ release over time. Conversely, for neutral liposomes containing TDB, although the initial amount of IFN-γ was slightly lower than the cationic equivalent, the overall protective immune responses of these neutral liposomes were effectively maintained over time, generating good levels of protection. To that end, although the addition of DSPC and Chol reduced the protective immunity of DDA:TDB liposomes, relatively high protection was observed for the neutral counterpart, DSPC:Chol:TDB, which may offer an effective neutral alternative to the DDA:TDB cationic system, especially for the delivery of either zwitterionic (neutral) or cationic molecules or antigens.

Topics: Adjuvants, Immunologic; Animals; Female; Glycolipids; Humans; Interferon-gamma; Liposomes; Mice; Mice, Inbred C57BL; Phosphatidylcholines; Quaternary Ammonium Compounds; Recombinant Fusion Proteins; Tuberculosis; Tuberculosis Vaccines; Vaccines, Subunit