Abstracts (complete list) - Wissenschaft Online

Verena Moos, Kristina Allers, Thomas Schneider
Impaired innate functions of monocytes and macrophages in
Whipple`s disease
Whipple`s disease is a rare chronic multisystemic infectious disease caused by the
actinomycete Tropheryma whipplei. Symptoms are heterogenous, but arthropathy,
weight loss, and diarrhea are present in most cases. Host factors like a reduced capacity
of T. whipplei-specific Th1 reactivity are suspected to be responsible for the
pathogenesis of Whipple`s disease. Monocytes and macrophages as important cells of
the innate immune response have been shown to be involved in the pathogenesis of
Whipple`s disease, but innate defense mechanism induced by T. whipplei were not
ivestigated so far. Therefore, we studied phagocytosis and the induction of oxidative
burst induced by T. whipplei in comparison to related and unrelated bacteria in fresh
blood of patients with Whipple´s disease. Analysis included serum concentration of
cyto- and chemokines indicative for macrophage activation, and the phenotypical
characterization of peripheral and duodenal macrophages.
T. whipplei is phagocytosed and induces a robust oxidative burst in monocytes of
healthy controls. However, Whipple`s disease patients showed reduced phagocytosis
and oxidative burst upon exposure to T. whipplei, whereas their capacity to react to
other related and not related bacteria was not reduced compared to controls.
Macrophages of Whipple´s disease patients reveal an alternatively activated phenotype
in vivo and in situ indicated by the expression of CD163, and the cytokine pattern in the
sera of Whipple´s disease patients. Hence, we conclude that ineffective innate defense
mechanism may be responsible for an impaired clearance of T. whipplei and might
initiate insufficient T. whipplei-specific T cell responses in Whipple`s disease patients.