title: Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation.
abstract: The disappearance and reformation of granulomas during tuberculosis has been described using PET/CT/X-ray in both human clinical settings and animal models, but the mechanisms of granuloma reformation during active disease remains unclear. Granulomas can recruit inflammatory dendritic cells (iDCs) that can regulate local T-cell responses and can carry bacteria into the lymph nodes, which is crucial for generating systemic T-cell responses against mycobacteria. Here, we report that a subset of mycobacterium-infected iDCs are associated with bacteria-specific T-cells in infected tissue, outside the granuloma, and that this results in the formation of new and/or larger multi-focal lesions. Mycobacterium-infected iDCs express less CCR7 and migrate less efficiently compared to the non-infected iDCs, which may support T-cell capture in granulomatous tissue. Capture may reduce antigen availability in the lymph node, thereby decreasing systemic priming, resulting in a possible regulatory loop between systemic T-cell responses and granuloma reformation. T-cell/infected iDCs clusters outside the granuloma can be detected during the acute and chronic phase of BCG and Mtb infection. Our studies suggest a direct role for inflammatory dendritic cells in the dissemination of granulomatous inflammation.
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin.|Cellular and Molecular Pathology Training Program, University of Wisconsin Madison.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Harding
authors.affiliation: Neuroscience Training Program, University of Wisconsin Madison.
authors.forename: Aditya
authors.initials: A
authors.lastname: Rayasam
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin.|Cellular and Molecular Pathology Training Program, University of Wisconsin Madison.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Schreiber
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin.|Cellular and Molecular Pathology Training Program, University of Wisconsin Madison.|Neuroscience Training Program, University of Wisconsin Madison.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fabry
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin.|Cellular and Molecular Pathology Training Program, University of Wisconsin Madison.
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D054421:Chemokine CCL21 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D011401:Promoter Regions, Genetic; D058525:Quartz Crystal Microbalance Techniques; D054400:Receptors, CCR7 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D039521:CD11c Antigen; D054421:Chemokine CCL21; D054400:Receptors, CCR7