The Experts below are selected from a list of 14730 Experts worldwide ranked by ideXlab platform

Henry W Boom - One of the best experts on this subject based on the ideXlab platform.

  • mycobacterium tuberculosis lipoprotein lprg rv1411c binds triacylated Glycolipid agonists of toll like receptor 2
    Nature Structural & Molecular Biology, 2010
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Ahmad R Arida, Henry W Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought to be dependent on its N-terminal triacylation. Unexpectedly, here we find that nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated MTB Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis.

Tanyun Cheng - One of the best experts on this subject based on the ideXlab platform.

  • Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated Glycolipid agonists of Toll-like receptor 2
    2016
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Ahmad R, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Henry Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (Mtb) in mice. Mtb lipoprotein LprG has TLR2 agonist activity, thought to be dependent on its N-terminal triacylation. Surprisingly, here we find that non-acylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated Mtb Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis

  • hiv disrupts human t cells that target mycobacterial Glycolipids
    The Journal of Infectious Diseases, 2016
    Co-Authors: Victoria Kasprowicz, Tanyun Cheng, Thumbi Ndungu, Henry Sunpath, Branch D Moody, Anne Kasmar
    Abstract:

    : Single-cell analysis captures the heterogeneity of T-cell populations that target defined antigens. Human immunodeficiency virus (HIV) infection results in defects of antimycobacterial immunity, which remain poorly defined. We therefore recruited a small number of subjects, including those with latent and active M. tuberculosis infection, with or without concomitant HIV infection, and tracked the mycobacterial Glycolipid-reactive T-cell repertoire by using CD1b tetramers. Glycolipid-reactive T cells expressed memory markers and the HIV coreceptors CD4 and CCR5; they were not detected in subjects with HIV-associated active M. tuberculosis infection. HIV infection may affect T cells that recognize mycobacterial Glycolipids and influence immunity.

  • mycobacterium tuberculosis lipoprotein lprg rv1411c binds triacylated Glycolipid agonists of toll like receptor 2
    Nature Structural & Molecular Biology, 2010
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Ahmad R Arida, Henry W Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought to be dependent on its N-terminal triacylation. Unexpectedly, here we find that nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated MTB Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis.

Branch D Moody - One of the best experts on this subject based on the ideXlab platform.

  • Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated Glycolipid agonists of Toll-like receptor 2
    2016
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Ahmad R, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Henry Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (Mtb) in mice. Mtb lipoprotein LprG has TLR2 agonist activity, thought to be dependent on its N-terminal triacylation. Surprisingly, here we find that non-acylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated Mtb Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis

  • hiv disrupts human t cells that target mycobacterial Glycolipids
    The Journal of Infectious Diseases, 2016
    Co-Authors: Victoria Kasprowicz, Tanyun Cheng, Thumbi Ndungu, Henry Sunpath, Branch D Moody, Anne Kasmar
    Abstract:

    : Single-cell analysis captures the heterogeneity of T-cell populations that target defined antigens. Human immunodeficiency virus (HIV) infection results in defects of antimycobacterial immunity, which remain poorly defined. We therefore recruited a small number of subjects, including those with latent and active M. tuberculosis infection, with or without concomitant HIV infection, and tracked the mycobacterial Glycolipid-reactive T-cell repertoire by using CD1b tetramers. Glycolipid-reactive T cells expressed memory markers and the HIV coreceptors CD4 and CCR5; they were not detected in subjects with HIV-associated active M. tuberculosis infection. HIV infection may affect T cells that recognize mycobacterial Glycolipids and influence immunity.

  • mycobacterium tuberculosis lipoprotein lprg rv1411c binds triacylated Glycolipid agonists of toll like receptor 2
    Nature Structural & Molecular Biology, 2010
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Ahmad R Arida, Henry W Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought to be dependent on its N-terminal triacylation. Unexpectedly, here we find that nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated MTB Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis.

Michael G. Drage - One of the best experts on this subject based on the ideXlab platform.

  • Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) binds triacylated Glycolipid agonists of Toll-like receptor 2
    2016
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Ahmad R, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Henry Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (Mtb) in mice. Mtb lipoprotein LprG has TLR2 agonist activity, thought to be dependent on its N-terminal triacylation. Surprisingly, here we find that non-acylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated Mtb Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis

  • mycobacterium tuberculosis lipoprotein lprg rv1411c binds triacylated Glycolipid agonists of toll like receptor 2
    Nature Structural & Molecular Biology, 2010
    Co-Authors: Michael G. Drage, Tanyun Cheng, Branch D Moody, Han-chun Tsai, Nicole D. Pecora, Supriya Shukla, Roxana E. Rojas, Chetan Seshadri, Ahmad R Arida, Henry W Boom
    Abstract:

    Knockout of lprG results in decreased virulence of Mycobacterium tuberculosis (MTB) in mice. MTB lipoprotein LprG has TLR2 agonist activity, which is thought to be dependent on its N-terminal triacylation. Unexpectedly, here we find that nonacylated LprG retains TLR2 activity. Moreover, we show LprG association with triacylated Glycolipid TLR2 agonists lipoarabinomannan, lipomannan and phosphatidylinositol mannosides (which share core structures). Binding of triacylated species was specific to LprG (not LprA) and increased LprG TLR2 agonist activity; conversely, association of Glycolipids with LprG enhanced their recognition by TLR2. The crystal structure of LprG in complex with phosphatidylinositol mannoside revealed a hydrophobic pocket that accommodates the three alkyl chains of the ligand. In conclusion, we demonstrate a Glycolipid binding function of LprG that enhances recognition of triacylated MTB Glycolipids by TLR2 and may affect Glycolipid assembly or transport for bacterial cell wall biogenesis.

Alice L. Yu - One of the best experts on this subject based on the ideXlab platform.

  • tailored design of nkt stimulatory Glycolipids for polarization of immune responses
    Journal of Biomedical Science, 2017
    Co-Authors: Jungtung Hung, Jingrong Huang, Alice L. Yu
    Abstract:

    Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with Glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known Glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory Glycolipids. Many analogues have been generated by modification of the galactosyl moiety, the acyl chain or the phytosphingosine chain of α-GalCer. Some of the analogues showed greater abilities than α-GalCer in polarizing immune responses toward Th1 or Th2 dominance. Among them, several analogues containing phenyl groups in the lipid tails were more potent in inducing Th1-skewed cytokines and exhibited greater anticancer efficacy than α-GalCer. Analyses of the correlation between structure and activity of various α-GalCer analogues on the activation of iNKT cell revealed that CD1d–Glycolipid complexes interacted with the same population of iNKT cell expressing similar T-cell receptor Vβ as α-GalCer. On the other hand, those phenyl Glycolipids with propensity for Th1 dominant responses showed greater binding avidity and stability than α-GalCer for iNKT T-cell receptor when complexed with CD1d. Thus, it is the avidity and stability of the ternary complexes of CD1d-Glycolipid-iNKT TCR that dictate the polarity and potency of immune responses. These findings provide a key to the rationale design of immune modulating Glycolipids with desirable Th1/Th2 polarity for clinical application. In addition, elucidation of α-GalCer-induced anergy, liver damage and accumulation of myeloid derived suppressor cells has offered explanation for its lacklustre anti-cancer activities in clinical trials. On other hand, the lack of such drawbacks in Glycolipid analogues containing phenyl groups in the lipid tails of α-GalCer coupled with the greater binding avidity and stability of CD1d-Glycolipid complex for iNKT T-cell receptor, account for their superior anti-cancer efficacy in tumor bearing mice. Further clinical development of these phenyl Glycolipids is warranted.

  • potent immune modulating and anticancer effects of nkt cell stimulatory Glycolipids
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Yajen Chang, Jingrong Huang, Jungtung Hung, Douglass Wu, Masakazu Fujio, Yichien Tsai, Chihuey Wong, Alice L. Yu
    Abstract:

    α-Galactosylceramide (α-GalCer), a Glycolipid that stimulates natural killer T (NKT) cells to produce both T helper (Th)1 and Th2 cytokines, has shown antitumor effects in mice but failed in clinical trials. We evaluated 16 analogs of α-GalCer for their CD1-mediated T cell receptor (TCR) activation of naive human NKT cells and their anticancer efficacy. In vitro, Glycolipids containing an aromatic ring in their acyl tail or sphingosine tail were more effective than α-GalCer in inducing Th1 cytokines/chemokines, TCR activation, and human NKT cell expansion. None of these Glycolipids could directly stimulate human dendritic cell maturation, except for a Glycolipid with an aromatic ring on the sphingosine tail. Here, we show that Glycolipids activated the TCR of NKT cells with phosphorylation of CD3e, ERK1/2, or CREB, which correlated with their induction of Th1 cytokines. Notably, the extent of NKT cell activation when Glycolipid was presented by antigen-presenting cells was greater than when Glycolipid was presented by non-antigen-presenting cells. In vivo, in mice bearing breast or lung cancers, the Glycolipids that induced more Th1-biased cytokines and CD8/CD4 T cells displayed significantly greater anticancer potency than α-GalCer. These findings indicate that α-GalCer analogs can be designed to favor Th1-biased immunity, with greater anticancer efficacy and other immune-enhancing activities than α-GalCer itself.