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

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Katina Schinnerling1, Anika Geelhaar-Karsch1, Kristina Allers1

  • 1Medizinische Klinik I, Charité-Universitätsmedizin Berlin, CBF, Berlin, Germany.

Infection and Immunity
|November 12, 2014
PubMed

Insights

Dendritic cells (DCs) in Whipple's disease are immature and produce less interleukin-12 (IL-12), impairing T cell responses. These dysfunctional DCs may help spread the Tropheryma whipplei bacterium.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Classical Whipple's disease (CWD) is characterized by Tropheryma whipplei-laden macrophages, impaired Th1 responses, and low IL-12 secretion.
  • Dendritic cells (DCs) play a crucial role in initiating adaptive immune responses, particularly T cell activation.

Purpose of the Study:

  • To investigate the composition, distribution, and functionality of dendritic cells (DCs) in patients with classical Whipple's disease (CWD).
  • To determine the role of DC dysfunction, specifically IL-12 production, in the impaired T cell response observed in CWD.

Main Methods:

  • Ex vivo and in vitro analysis of DC populations using fluorescence-activated cell sorting (FACS) and immunohistochemistry.
  • Assessment of DC maturation markers (CD83, CD86, CCR7) and cytokine production (IL-12) following stimulation.
  • Evaluation of T cell activation capacity and T. whipplei-specific Th1 responses.

Main Results:

  • Peripheral myeloid DCs (M-DCs) were reduced in untreated CWD patients, exhibiting an immature phenotype with decreased maturation markers.
  • In vitro-generated DCs from CWD patients showed impaired IL-12 production and failed to activate T. whipplei-specific Th1 cells, despite normal maturation and T cell-stimulatory capacity.
  • Immature DC-SIGN(+) DCs containing T. whipplei were observed in duodenal and lymphoid tissues; lymph nodes showed reduced DCs and proliferating lymphocytes.

Conclusions:

  • Dysfunctional IL-12 production by DCs in CWD creates suboptimal conditions for priming T. whipplei-specific T cells.
  • Immature DCs harboring T. whipplei may contribute to the dissemination of the bacterium, exacerbating the disease.
  • DC dysfunction is a key factor in the immunopathogenesis of classical Whipple's disease.

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