title: Inflammatory dendritic cells migrate in and out of transplanted chronic mycobacterial granulomas in mice.
abstract: An estimated one-third of the world's population is infected with Mycobacterium tuberculosis, although most affected individuals maintain a latent infection. This control is attributed to the formation of granulomas, cell masses largely comprising infected macrophages with T cells aggregated around them. Inflammatory DCs, characterized as CD11c+CD11b+Ly6C+, are also found in granulomas and are an essential component of the acute immune response to mycobacteria. However, their function during chronic infection is less well understood. Here, we report that CD11c+ cells dynamically traffic in and out of both acute and chronic granulomas induced by Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) in mice. By transplanting Mycobacterium-induced granulomas containing fluorescently labeled CD11c+ cells and bacteria into unlabeled mice, we were able to follow CD11c+ cell trafficking and T cell activation. We found that half of the CD11c+ cells in chronic granulomas were exchanged within 1 week. Compared with tissue-resident DC populations, CD11c+ cells migrating out of granuloma-containing tissue had an unexpected systemic dissemination pattern. Despite low antigen availability, systemic CD4+ T cell priming still occurred during chronic infection. These data demonstrate that surveillance of granulomatous tissue by CD11c+ cells is continuous and that these cells are distinct from tissue-resident DC populations and support T cell priming during both stages of Mycobacterium infection. This intense DC surveillance may also be a feature of Mycobacterium tuberculosis infection and other granuloma-associated diseases.
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Schreiber
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Harding
authors.forename: Oliver
authors.initials: O
authors.lastname: Hunt
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Altamirano
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hulseberg
authors.forename: Danielle
authors.initials: D
authors.lastname: Stewart
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fabry
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology* / Q000502:physiology; D004195:Disease Models, Animal; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009164:Mycobacterium Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D009163:Mycobacterium bovis / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D039521:CD11c Antigen