Role of Dendritic Cells in the Pathogenesis of Whipple's Disease
| Autor: | Katina Schinnerling, Anja A. Kühl, Anika Geelhaar-Karsch, Christoph Loddenkemper, Verena Moos, Kristina Allers, Ralf Ignatius, Ulrike Erben, Kristina Conrad, Julian Friebel, Thomas Schneider |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Receptors CCR7 Duodenum animal diseases Immunology Tropheryma Immunoglobulins Priming (immunology) CD11c Receptors Cell Surface C-C chemokine receptor type 7 Biology Lymphocyte Activation Microbiology Interleukin-12 Subunit p35 Proinflammatory cytokine Antigens CD medicine Humans Lectins C-Type Whipple's disease Aged Cell Proliferation Aged 80 and over CD86 Membrane Glycoproteins Macrophages Whipple Disease Dendritic Cells Bacterial Infections Dendritic cell Middle Aged Th1 Cells Flow Cytometry medicine.disease CD11c Antigen Infectious Diseases Female Parasitology B7-2 Antigen Lymph Nodes Cell Adhesion Molecules |
| Zdroj: | Infection and Immunity. 83:482-491 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.02463-14 |
| Popis: | Accumulation of Tropheryma whipplei -stuffed macrophages in the duodenum, impaired T. whipplei -specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex vivo or after in vitro maturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistry in situ . A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11c high myeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype. In vitro -generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activate T. whipplei -specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN + DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei -specific T cells during CWD and that immature DC carrying T. whipplei contribute to the dissemination of the bacterium. |
| Databáze: | OpenAIRE |
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