title: Mycobacterium bovis Bacillus Calmette-Guerin infects DC-SIGN- dendritic cell and causes the inhibition of IL-12 and the enhancement of IL-10 production.
abstract: The only available vaccine against tuberculosis is Mycobacterium bovis Bacillus Calmette Guérin (BCG), although its efficacy in preventing pulmonary tuberculosis is controversial. Early interactions between dendritic cells (DC) and BCG or Mycobacterium tuberculosis (Mtb) are thought to be critical for mounting a protective antimycobacterial immune response. Recent studies have shown that BCG and Mtb target the DC-specific C-type lectin intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) to infect DC and inhibit their immunostimulatory function. This would occur through the interaction of the mycobacterial mannosylated lipoarabinomannan to DC-SIGN, which would prevent DC maturation and induce the immunosuppressive cytokine interleukin (IL)-10 synthesis. Here, we confirm that DC-SIGN is expressed in DC derived from monocytes cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-4 and show that it is not expressed in DC derived from monocytes cultured in GM-CSF and interferon-alpha (IFN-alpha). We also demonstrate that DC-SIGN(-) DC cultured in GM-CSF and IFN-alpha are able to phagocytose BCG and to undergo a maturation program as well as DC-SIGN(+) DC cultured in IL-4 and GM-CSF. We also show that BCG causes the impairment of IL-12 and the induction of IL-10 secretion by DC, irrespective of DC-SIGN expression. Finally, we demonstrate that the capacity to stimulate a mixed leukocyte reaction of naïve T lymphocytes is not altered by the treatment of both DC populations with BCG. These data suggest that DC-SIGN cannot be considered as the unique DC receptor for BCG internalization, and it is more interesting that the mycobacteria-induced immunosuppression cannot be attributed to the engagement of a single receptor.
authors.affiliation: Dipartimento Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gagliardi
authors.forename: Raffaela
authors.initials: R
authors.lastname: Teloni
authors.forename: Federico
authors.initials: F
authors.lastname: Giannoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardini
authors.forename: Valeria
authors.initials: V
authors.lastname: Sargentini
authors.forename: Lara
authors.initials: L
authors.lastname: Brunori
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Fattorini
authors.forename: Roberto
authors.initials: R
authors.lastname: Nisini
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D015536:Down-Regulation / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009163:Mycobacterium bovis / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D001428:Bacterial Vaccines; D015815:Cell Adhesion Molecules; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016898:Interferon-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin