| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of Medicine and Molecular Virology, Immunology, and Medical Genetics, Center for Microbial Interface Biology, and Division of Infectious Diseases, Ohio State University, Columbus, OH 43210
The Mycobacterium tuberculosis (M.tb) envelope is highly mannosylated with phosphatidyl-myo-inositol mannosides (PIMs), lipomannan, and mannose-capped lipoarabinomannan (ManLAM). Little is known regarding the interaction between specific PIM types and host cell C-type lectin pattern recognition receptors. The macrophage mannose receptor (MR) and dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells engage ManLAM mannose caps and regulate several host responses. In this study, we analyzed the association of purified PIM families (f, separated by carbohydrate number) and individual PIM species (further separated by fatty acid number) from M.tb H37Rv with human monocyte-derived macrophages (MDMs) and lectin-expressing cell lines using an established bead model. Higher-order PIMs preferentially associated with the MR as demonstrated by their reduced association with MDMs upon MR blockade and increased binding to COS-1-MR. In contrast, the lower-order PIM2f associated poorly with MDMs and did not bind to COS-1-MR. Triacylated PIM species were recognized by MDM lectins better than tetra-acylated species and the degree of acylation influenced higher-order PIM association with the MR. Moreover, only higher-order PIMs that bind the MR showed a significant increase in phagosome-lysosome fusion upon MR blockade. In contrast with the MR, the PIM2f and lipomannan were recognized by DC-SIGN comparable to higher-order PIMs and ManLAM, and the association was independent of their degree of acylation. Thus, recognition of M.tb PIMs by host cell C-type lectins is dependent on both the nature of the terminal carbohydrates and degree of acylation. Subtle structural differences among the PIMs impact host cell recognition and response and are predicted to influence the intracellular fate of M.tb.
This article has been cited by other articles:
|
|
 |
|
  T. K Carlson, J. B Torrelles, K. Smith, T. Horlacher, R. Castelli, P. H Seeberger, E. C Crouch, and L. S Schlesinger Critical role of amino acid position 343 of surfactant protein-D in the selective binding of glycolipids from Mycobacterium tuberculosis Glycobiology, December 1, 2009; 19(12): 1473 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Geurtsen, S. Chedammi, J. Mesters, M. Cot, N. N. Driessen, T. Sambou, R. Kakutani, R. Ummels, J. Maaskant, H. Takata, et al. Identification of Mycobacterial {alpha}-Glucan As a Novel Ligand for DC-SIGN: Involvement of Mycobacterial Capsular Polysaccharides in Host Immune Modulation J. Immunol., October 15, 2009; 183(8): 5221 - 5231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. N. Driessen, R. Ummels, J. J. Maaskant, S. S. Gurcha, G. S. Besra, G. D. Ainge, D. S. Larsen, G. F. Painter, C. M. J. E. Vandenbroucke-Grauls, J. Geurtsen, et al. Role of Phosphatidylinositol Mannosides in the Interaction between Mycobacteria and DC-SIGN Infect. Immun., October 1, 2009; 77(10): 4538 - 4547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Doz, S. Rose, N. Court, S. Front, V. Vasseur, S. Charron, M. Gilleron, G. Puzo, I. Fremaux, Y. Delneste, et al. Mycobacterial Phosphatidylinositol Mannosides Negatively Regulate Host Toll-like Receptor 4, MyD88-dependent Proinflammatory Cytokines, and TRIF-dependent Co-stimulatory Molecule Expression J. Biol. Chem., August 28, 2009; 284(35): 23187 - 23196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B Torrelles, L. E DesJardin, J. MacNeil, T. M Kaufman, B. Kutzbach, R. Knaup, T. R McCarthy, S. S Gurcha, G. S Besra, S. Clegg, et al. Inactivation of Mycobacterium tuberculosis mannosyltransferase pimB reduces the cell wall lipoarabinomannan and lipomannan content and increases the rate of bacterial-induced human macrophage cell death Glycobiology, July 1, 2009; 19(7): 743 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Azad, J. B. Torrelles, and L. S. Schlesinger Mutation in the DC-SIGN cytoplasmic triacidic cluster motif markedly attenuates receptor activity for phagocytosis and endocytosis of mannose-containing ligands by human myeloid cells J. Leukoc. Biol., December 1, 2008; 84(6): 1594 - 1603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Torrelles, R. Knaup, A. Kolareth, T. Slepushkina, T. M. Kaufman, P. Kang, P. J. Hill, P. J. Brennan, D. Chatterjee, J. T. Belisle, et al. Identification of Mycobacterium tuberculosis Clinical Isolates with Altered Phagocytosis by Human Macrophages Due to a Truncated Lipoarabinomannan J. Biol. Chem., November 14, 2008; 283(46): 31417 - 31428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Doz, S. Rose, J. Nigou, M. Gilleron, G. Puzo, F. Erard, B. Ryffel, and V. F. J. Quesniaux Acylation Determines the Toll-like receptor (TLR)-dependent Positive Versus TLR2-, Mannose Receptor-, and SIGNR1-independent Negative Regulation of Pro-inflammatory Cytokines by Mycobacterial Lipomannan J. Biol. Chem., September 7, 2007; 282(36): 26014 - 26025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pompei, S. Jang, B. Zamlynny, S. Ravikumar, A. McBride, S. P. Hickman, and P. Salgame Disparity in IL-12 Release in Dendritic Cells and Macrophages in Response to Mycobacterium tuberculosis Is Due to Use of Distinct TLRs J. Immunol., April 15, 2007; 178(8): 5192 - 5199. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
