title: Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii.
abstract: 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.
authors.affiliation: Department of Medicine, University of Zurich Medical School, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Schoedon
authors.forename: D
authors.initials: D
authors.lastname: Goldenberger
authors.forename: R
authors.initials: R
authors.lastname: Forrer
authors.forename: A
authors.initials: A
authors.lastname: Gunz
authors.forename: F
authors.initials: F
authors.lastname: Dutly
authors.forename: M
authors.initials: M
authors.lastname: Höchli
authors.forename: M
authors.initials: M
authors.lastname: Altwegg
authors.forename: A
authors.initials: A
authors.lastname: Schaffner
mesh_terms: D039903:Actinobacteria / Q000254:growth & development / Q000302:isolation & purification*; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D008061:Whipple Disease / Q000382:microbiology* / Q000473:pathology
chemical_list: D003470:Culture Media; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone