title: Dendritic cells recruited to the lung shortly after intranasal delivery of Mycobacterium bovis BCG drive the primary immune response towards a type 1 cytokine production.
abstract: We showed in a previous study that the intranasal (i.n) delivery of bacille Calmette-Guérin (BCG) to BP2 mice (H-2q) inhibits eosinophilia and bronchial hyperreactivity in a mouse model of asthma. The present work has been performed to characterize the leucocyte lineages recruited to the lungs of mice after i.n. delivery of BCG and potentially involved in the polarization of T lymphocytes. The different antigen-presenting cells (APC) recruited to bronchoalveolar lavage (BAL) and to lung tissue of mice shortly after the delivery of BCG were analysed in parallel as well as their capacity to drive the immune response towards a T helper type 1 cytokine production. Alveolar macrophages (AM) from the BAL were CD11c+, F4/80+ and CD11b-, and in the lung tissue two major populations of potential APC were detected: one CD11c-, F4/80+, CD11b+ and I-Aq- was identified as interstitial macrophages (IM) and a second expressing CD11c+ and I-Aq+ antigens, negative for CD11b and F4/80 markers as leucocytic dendritic cells (DC). Freshly isolated DC up-regulated CD11b and CD40 antigens after overnight culture, but remained negative for CD8alpha antigen, suggesting a myeloid origin. Lung DC which produced high amount of interleukin (IL)-12 were potent inducers of naive CD4+ T lymphocyte priming, as assessed by interferon-gamma (IFN-gamma) production by these naive CD4+ T cells. Lung explants recovered long term after BCG delivery produced sustained levels of IFN-gamma. Our results suggest that AM and particularly DC by secreting IL-12 shortly after BCG delivery induce the long-term persistence of IFN-gamma-secreting T cells percolating in BCG-loaded lung tissue.
authors.affiliation: Département de Médecine Moléculaire, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Micheline
authors.initials: M
authors.lastname: Lagranderie
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Balazuc
authors.forename: Hélène
authors.initials: H
authors.lastname: Kiefer-Biasizzo
authors.forename: Jose-Roberto
authors.initials: JR
authors.lastname: Lapa e Silva
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Gilles
authors.initials: G
authors.lastname: Marchal
authors.forename: Boris B
authors.initials: BB
authors.lastname: Vargaftig
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis / Q000276:immunology; D014373:Tuberculin / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D015848:Interleukin-5; D014373:Tuberculin; D018664:Interleukin-12; D007371:Interferon-gamma