Role of dendritic cells in the pathogenesis of whipple's disease

Katina Schinnerling, Anika Geelhaar-Karsch, Kristina Allers, Julian Friebel, Kristina Conrad, Christoph Loddenkemper, Anja A. Kühl, Ulrike Erben, Ralf Ignatius, Verena Moos, Thomas Schneider

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

12 Citas (Scopus)

Resumen

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 CD11chigh 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.

Idioma originalInglés
Páginas (desde-hasta)482-491
Número de páginas10
PublicaciónInfection and Immunity
Volumen83
N.º2
DOI
EstadoPublicada - 2015
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Parasitología
  • Microbiología
  • Inmunología
  • Enfermedades infecciosas

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