title: Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing major histocompatibility complex class II molecules capable of antigen presentation.
abstract: Major histocompatibility complex class II (MHC-II) molecules are released by murine macrophages upon lipopolysaccharide (LPS) stimulation and ATP signaling through the P2X7 receptor. These studies show that infection of macrophages with Mycobacterium tuberculosis or M. bovis strain BCG enhances MHC-II release in synergy with ATP. Shed MHC-II was contained in two distinct organelles, exosomes and plasma membrane-derived microvesicles, which were both able to present exogenous antigenic peptide to T hybridoma cells. Furthermore, microvesicles from mycobacterium-infected macrophages were able to directly present M. tuberculosis antigen (Ag) 85B(241-256)-I-A(b) complexes that were generated by the processing of M. tuberculosis Ag 85B in infected cells to both M. tuberculosis-specific T hybridoma cells and naïve P25 M. tuberculosis T-cell receptor (TCR)-transgenic T cells. In the presence of prefixed macrophages, exosomes from mycobacterium-infected macrophages provided weak stimulation to M. tuberculosis-specific T hybridoma cells but not naïve P25 T cells. Thus, infection with M. tuberculosis primes macrophages for the increased release of exosomes and microvesicles bearing M. tuberculosis peptide-MHC-II complexes that may generate antimicrobial T-cell responses.
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4943, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Ramachandra
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Colleen J
authors.initials: CJ
authors.lastname: Lewis
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: George R
authors.initials: GR
authors.lastname: Dubyak
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology / Q000502:physiology*; D015153:Blotting, Western; D055354:Exosomes / Q000276:immunology / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000502:physiology; D006825:Hybridomas / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009163:Mycobacterium bovis / Q000378:metabolism / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000502:physiology; D058486:Receptors, Purinergic P2X7 / Q000502:physiology; D022142:Secretory Vesicles / Q000276:immunology / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology / Q000503:physiopathology
chemical_list: D000949:Histocompatibility Antigens Class II; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate