Polyclonal activation of naïve T cells by urease deficient-recombinant BCG that produced protein complex composed of heat shock protein 70, CysO and major membrane protein-II.
Background: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is known to be only partially effective in inhibiting M. tuberculosis (MTB) multiplication in human. A new recombinant (r) urease-deficient BCG (BCG-dHCM) that secretes protein composed of heat shock protein (HSP)70, MTB-derived CysO and...
| Publicado en: | BMC Infectious Diseases Vol. 14; no. 1; pp. 179 - 180 |
|---|---|
| Autores principales: | , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
2014
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=109752257&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 109752257 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14712334 1CHU jtl: BMC Infectious Diseases issn: 14712334 maglogo: N pubinfo: dt: 2014 vid: 14 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 109752257 NLM24690183 2012602275 10.1186/1471-2334-14-179 NLM24690183 PMC4011778 109752257 ppf: 179 ppct: 1 formats: tig: atl: Polyclonal activation of naïve T cells by urease deficient-recombinant BCG that produced protein complex composed of heat shock protein 70, CysO and major membrane protein-II. aug: au: Tsukamoto, Yumiko Maeda, Yumi Tamura, Toshiki Mukai, Tetsu Makino, Masahiko affil: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan. ytsuka@nih.go.jp. sug: subj: Antigens, Bacterial Immunology Bacterial Proteins Immunology BCG Vaccine Immunology Immunologic Techniques Mycobacterium Immunology Urease Deficiency Animal Studies Bacterial Proteins Metabolism Cytokines Immunology Cytokines Metabolism Dendritic Cells Immunology Human Interferons Immunology Interferons Metabolism Macrophages Immunology Membrane Proteins Immunology Membrane Proteins Metabolism Mice Mycobacterium Mycobacterium Tuberculosis Immunology Mycobacterium Metabolism Proteins Immunology Proteins Metabolism Recombinant Proteins Immunology T Lymphocytes Immunology ab: Background: Mycobacterium bovis bacillus Calmette-Guérin (BCG) is known to be only partially effective in inhibiting M. tuberculosis (MTB) multiplication in human. A new recombinant (r) urease-deficient BCG (BCG-dHCM) that secretes protein composed of heat shock protein (HSP)70, MTB-derived CysO and major membrane protein (MMP)-II was produced for the efficient production of interferon gamma (IFN-γ) which is an essential element for mycobacteriocidal action and inhibition of neutrophil accumulation in lungs.Methods: Human monocyte-derived dendritic cells (DC) and macrophages were differentiated from human monocytes, infected with BCG and autologous T cells-stimulating activity of different constructs of BCG was assessed. C57BL/6 mice were used to test the effectiveness of BCG for the production of T cells responsive to MTB-derived antigens (Ags).Results: BCG-dHCM intracellularly secreted HSP70-CysO-MMP-II fusion protein, and activated DC by up-regulating Major Histcompatibility Complex (MHC), CD86 and CD83 molecules and enhanced various cytokines production from DC and macrophages. BCG-dHCM activated naïve T cells of both CD4 and CD8 subsets through DC, and memory type CD4+ T cells through macrophages in a manner dependent on MHC and CD86 molecules. These T cell activations were inhibited by the pre-treatment of Ag-presenting cells (APCs) with chloroquine. The single and primary BCG-dHCM-inoculation produced long lasting T cells responsive to in vitro secondarily stimulation with HSP70, CysO, MMP-II and H37Rv-derived cytosolic protein, and partially inhibited the replication of aerosol-challenged MTB.Conclusions: The results indicate that introduction of different type of immunogenic molecules into a urease-deficient rBCG is useful for providing polyclonal T cell activating ability to BCG and for production of T cells responsive to secondary stimulation. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|