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

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 specifi...

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Bibliographic Details
Published in:Immunology 2007-08, Vol.121 (4), p.462-472
Main Authors: Motta, Adriana, Schmitz, Carla, Rodrigues, Luiz, Ribeiro, Flávia, Teixeira, Cesar, Detanico, Thiago, Bonan, Carla, Zwickey, Heather, Bonorino, Cristina
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - immunology
Cell Proliferation
Cells, Cultured
cytokines
dendritic cells
Dendritic Cells - cytology
Dendritic Cells - immunology
heat-shock protein 70
Hematopoietic Stem Cells - immunology
HSP70 Heat-Shock Proteins - immunology
Interleukin-10 - biosynthesis
Lipopolysaccharides - immunology
Mice
Mice, Inbred C57BL
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Original
Phytohemagglutinins - immunology
T-cell proliferation
T-Lymphocytes - immunology
Tumor Necrosis Factor-alpha - biosynthesis
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Summary: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-α 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.
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1365-2567.2007.02564.x