title: Phosphatidylinositol mannoside from Mycobacterium tuberculosis binds alpha5beta1 integrin (VLA-5) on CD4+ T cells and induces adhesion to fibronectin.
abstract: The pathological hallmark of the host response to Mycobacterium tuberculosis is the granuloma where T cells and macrophages interact with the extracellular matrix (ECM) to control the infection. Recruitment and retention of T cells within inflamed tissues depend on adhesion to the ECM. T cells use integrins to adhere to the ECM, and fibronectin (FN) is one of its major components. We have found that the major M. tuberculosis cell wall glycolipid, phosphatidylinositol mannoside (PIM), induces homotypic adhesion of human CD4+ T cells and T cell adhesion to immobilized FN. Treatment with EDTA and cytochalasin D prevented PIM-induced T cell adhesion. PIM-induced T cell adhesion to FN was blocked with mAbs against alpha5 integrin chain and with RGD-containing peptides. Alpha5beta1 (VLA-5) is one of two major FN receptors on T cells. PIM was found to bind directly to purified human VLA-5. Thus, PIM interacts directly with VLA-5 on CD4+ T lymphocytes, inducing activation of the integrin, and promoting adhesion to the ECM glycoprotein, FN. This is the first report of direct binding of a M. tuberculosis molecule to a receptor on human T cells resulting in a change in CD4+ T cell function.
authors.affiliation: Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, OH 44106, USA. rxr38@cwru.edu
authors.forename: Roxana E
authors.initials: RE
authors.lastname: Rojas
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Thomas
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gehring
authors.forename: Preston J
authors.initials: PJ
authors.lastname: Hill
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002413:Cations, Divalent / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000302:isolation & purification / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002413:Cations, Divalent; D005353:Fibronectins; D039081:Integrin alpha5beta1; D009842:Oligopeptides; D010716:Phosphatidylinositols; C034154:phosphatidylinositol mannoside; C047981:arginyl-glycyl-aspartic acid