Fate of Mycobacterium tuberculosis within Murine Dendritic Cells

ABSTRACT The interaction of microbes with dendritic cells (DCs) is likely to have an enormous impact on the initiation of the immune response against a pathogen. In this study, we compared the interaction ofMycobacterium tuberculosis with murine bone marrow-derived DCs and macrophages (Mφ) in vitro. M. tuberculosis grew equally well within nonactivated DCs and Mφ. Activation of DCs and Mφ with gamma interferon and lipopolysaccharide inhibited the growth of the intracellular bacteria in a nitric oxide synthase-dependent fashion. However, while this activation enabled Mφ to kill the intracellular bacteria, the M. tuberculosis bacilli within activated DCs were not killed. Thus, DCs could restrict the growth of the intracellular mycobacteria but were less efficient than Mφ at eliminating the infection. These results may have implications for priming immune responses to M. tuberculosis. In addition, they suggest that DCs may serve as a reservoir for M. tuberculosis in tissues, including the lymph nodes and lungs.

[1]  Donald E. Broadbent,et al.  Memories are made of this , 1977, Nature.

[2]  G. Rook,et al.  AN ISOTOPE INCORPORATION ASSAY FOR THE ANTI-MYCOBACTERIAL EFFECTS OF HUMAN-MONOCYTES , 1981 .

[3]  I. Orme,et al.  Adoptive protection of the Mycobacterium tuberculosis-infected lung. Dissociation between cells that passively transfer protective immunity and those that transfer delayed-type hypersensitivity to tuberculin. , 1984, Cellular immunology.

[4]  B. Champion,et al.  I-A restricted activation by T cell lines of anti-tuberculosis activity in murine macrophages. , 1985, Clinical and experimental immunology.

[5]  D. Gray,et al.  T cell memory is short-lived in the absence of antigen , 1988, Nature.

[6]  Graham,et al.  T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis , 1989, Infection and immunity.

[7]  S. Kaufmann,et al.  Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates , 1991, Infection and immunity.

[8]  M. Denis.  Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. , 1991, Cellular immunology.

[9]  J. Flynn,et al.  Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  B. Bloom,et al.  Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages , 1992, The Journal of experimental medicine.

[11]  E. Hoefsmit,et al.  Effect of Bacillus Calmette-Guérin inoculation on numbers of dendritic cells in bronchoalveolar lavages of rats. , 1992, Immunobiology.

[12]  C. Sousa,et al.  Phagocytosis of antigens by Langerhans cells in vitro , 1993, The Journal of experimental medicine.

[13]  M. Röllinghoff,et al.  Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells , 1993, European journal of immunology.

[14]  R. Steinman,et al.  Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo , 1993, The Journal of experimental medicine.

[15]  M. Raviglione,et al.  Global tuberculosis incidence and mortality during 1990-2000. , 1994, Bulletin of the World Health Organization.

[16]  S. Kaufmann,et al.  Immune Mechanisms of Protection , 1994 .

[17]  B. Bloom,et al.  Tuberculosis Pathogenesis, Protection, and Control , 1994 .

[18]  J. Ellner,et al.  T-Cell Responses and Cytokines , 1994 .

[19]  K. Timmis,et al.  Invasion and intracellular survival of Bordetella bronchiseptica in mouse dendritic cells , 1994, Infection and immunity.

[20]  Polly Matzinger,et al.  Memories are made of this? , 1994, Nature.

[21]  M. Ernst,et al.  Defective antigen presentation by Mycobacterium tuberculosis-infected monocytes , 1994, Infection and immunity.

[22]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[23]  M. Röllinghoff,et al.  Dendritic cells in Leishmania major‐immune mice harbor persistent parasites and mediate an antigen‐specific T cell immune response , 1995, European journal of immunology.

[24]  R. Steinman,et al.  The endocytic activity of dendritic cells , 1995, The Journal of experimental medicine.

[25]  R. Kradin,et al.  The antigen-presenting activities of Ia+ dendritic cells shift dynamically from lung to lymph node after an airway challenge with soluble antigen , 1995, The Journal of experimental medicine.

[26]  K. Tanaka,et al.  Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis , 1995, Infection and immunity.

[27]  C Danieli,et al.  Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products , 1995, The Journal of experimental medicine.

[28]  C. Nathan,et al.  Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase , 1995, Cell.

[29]  K. Timmis,et al.  Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes , 1996, Molecular microbiology.

[30]  Matthias Abend,et al.  Tuberculosis: Pathogenesis, Protection and Control , 1996, Nature Medicine.

[31]  A. Lanzavecchia,et al.  Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation , 1996, The Journal of experimental medicine.

[32]  K. Rock,et al.  Major histocompatibility class I presentation of soluble antigen facilitated by Mycobacterium tuberculosis infection. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  H. Joller,et al.  Human dendritic cells phagocytose and process Borrelia burgdorferi. , 1996, Journal of immunology.

[34]  P. Ricciardi-Castagnoli,et al.  The role of cytokines in functional regulation and differentiation of dendritic cells. , 1996, Immunobiology.

[35]  B. Stockinger,et al.  Bone marrow-derived dendritic cells can process bacteria for MHC-I and MHC-II presentation to T cells. , 1997, Journal of immunology.

[36]  P. Ricciardi-Castagnoli,et al.  Dendritic cell maturation is required for initiation of the immune response , 1997, Journal of leukocyte biology.

[37]  L. Lu,et al.  Generation of nitric oxide by mouse dendritic cells and its implications for immune response regulation. , 1997, Advances in experimental medicine and biology.

[38]  Simon C Watkins,et al.  Activation of human dendritic cells following infection with Mycobacterium tuberculosis. , 1997, Journal of immunology.

[39]  P. Ricciardi-Castagnoli,et al.  CD14 is expressed by subsets of murine dendritic cells and upregulated by lipopolysaccharide. , 1997, Advances in experimental medicine and biology.

[40]  M. Mbow,et al.  Borrelia burgdorferi-pulsed dendritic cells induce a protective immune response against tick-transmitted spirochetes , 1997, Infection and immunity.

[41]  K. Kelly,et al.  Internalization of Chlamydia by dendritic cells and stimulation of Chlamydia-specific T cells. , 1998, Journal of immunology.

[42]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[43]  P. Kaye,et al.  Dendritic cells, but not macrophages, produce IL‐12 immediately following Leishmania donovani infection , 1998, European journal of immunology.

[44]  K. Lukacs,et al.  Protection against Mycobacterium tuberculosisInfection by CD8+ T Cells Requires the Production of Gamma Interferon , 1998, Infection and Immunity.

[45]  S. Mummidi,et al.  Human dendritic cell (DC)-based anti-infective therapy: engineering DCs to secrete functional IFN-gamma and IL-12. , 1998, Journal of immunology.

[46]  H. Caldwell,et al.  Chlamydial Infection in Inducible Nitric Oxide Synthase Knockout Mice , 1998, Infection and Immunity.

[47]  N. Reiner,et al.  Attenuation of HLA-DR expression by mononuclear phagocytes infected with Mycobacterium tuberculosis is related to intracellular sequestration of immature class II heterodimers. , 1998, Journal of immunology.

[48]  J. Flynn,et al.  Early Emergence of CD8+ T Cells Primed for Production of Type 1 Cytokines in the Lungs of Mycobacterium tuberculosis-Infected Mice , 1999, Infection and Immunity.

[49]  C. Demangel,et al.  Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guérin‐infected dendritic cells , 1999, European journal of immunology.

[50]  R. Brunham,et al.  Immunity to Chlamydia trachomatis mouse pneumonitis induced by vaccination with live organisms correlates with early granulocyte-macrophage colony-stimulating factor and interleukin-12 production and with dendritic cell-like maturation. , 1999, Infection and immunity.

[51]  Chyung-Ru Wang,et al.  Susceptibility of Mice Deficient in CD1D or TAP1 to Infection with Mycobacterium tuberculosis , 1999, The Journal of experimental medicine.

[52]  V. Verhasselt,et al.  Trypanosoma cruzi Infects Human Dendritic Cells and Prevents Their Maturation: Inhibition of Cytokines, HLA-DR, And Costimulatory Molecules , 1999, Infection and Immunity.

[53]  G. Zhong,et al.  Interleukin-12 production is required for chlamydial antigen-pulsed dendritic cells to induce protection against live Chlamydia trachomatis infection. , 1999, Infection and immunity.

[54]  A. Pain,et al.  Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells , 1999, Nature.

[55]  J. Flynn,et al.  Mice deficient in CD4 T cells have only transiently diminished levels of IFN-gamma, yet succumb to tuberculosis. , 1999, Journal of immunology.

[56]  T. Hammond,et al.  Salmonella efficiently enter and survive within cultured CD11c+ dendritic cells initiating cytokine expression , 1999, European journal of immunology.

[57]  C. Harding,et al.  Mycobacterium tuberculosis inhibits MHC class II antigen processing in murine bone marrow macrophages. , 1998, Cellular immunology.

[58]  M. Colston,et al.  Mycobacterium tuberculosis‐activated dendritic cells induce protective immunityin mice , 2000, Immunology.