Deactivation of Macrophages with Interleukin-4 Is the Key to the Isolation of Tropheryma whippelii
Schoedon, Gabriele ; Goldenberger, Daniel ; Forrer, Regula ; Gunz, Anja ; Dutly, Fabrizio ; Höchli, Mathias ; Altwegg, Martin ; Schaffner, Andreas
In: Journal of Infectious Diseases, 1997, vol. 176, no. 3, p. 672-677
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- Whipple's disease is a systemic illness caused by a specific agent. Despite recognition of bacteria in lesions, efforts to isolate the causative agent remained futile. A novel strategy was devised to culture Whipple bacilli in deactivated mononuclear phagocytes. Infected tissue was inoculated into human phagocytes deactivated with interleukin (IL)-4, IL-10, and dexamethasone. Within 8-10 days, diastase-resistant periodic acid-Schiff-positive inclusions appeared, corresponding to intact and degenerating bacteria shown to be Tropheryma whippelii by electron microscopy and molecular analyses. T. whippelii was passaged several times in deactivated monocytes and a monoblastic cell line. Time-kinetics growth studies and comparative polymerase chain reaction analysis documented multiplication of T. whippelii in deactivated macrophages. Complementary studies showed that IL-4 rendered phagocytes permissive for T. whippelii, a strong indication that host factors contribute to the pathogenesis of Whipple's disease. The propagation of T. whippelii will permit microbiologic, immunologic, seroepidemiologic, and therapeutic studies of this pathogen