title: Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro.
abstract: In different inflammatory disease models, heat-shock proteins (hsp) and hsp-derived peptides have been demonstrated to possess anti-inflammatory properties. While some studies have shown that hsp can directly interact with antigen-presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS-free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS-free TBhsp70 inhibits murine DC maturation in vitro, while LPS-contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor-alpha production by DC, but interleukin-10. In vivo, only LPS-contaminated TBhsp70 induces up-regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin-induced T-cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties.
authors.affiliation: Faculdade de Biociências e Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Motta
authors.forename: Carla
authors.initials: C
authors.lastname: Schmitz
authors.forename: Luiz
authors.initials: L
authors.lastname: Rodrigues
authors.forename: Flávia
authors.initials: F
authors.lastname: Ribeiro
authors.forename: Cesar
authors.initials: C
authors.lastname: Teixeira
authors.forename: Thiago
authors.initials: T
authors.lastname: Detanico
authors.forename: Carla
authors.initials: C
authors.lastname: Bonan
authors.forename: Heather
authors.initials: H
authors.lastname: Zwickey
authors.forename: Cristina
authors.initials: C
authors.lastname: Bonorino
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10