Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii.
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.
Schoedon
G
G
Department of Medicine, University of Zurich Medical School, Switzerland.
Goldenberger
D
D
Forrer
R
R
Gunz
A
A
Dutly
F
F
Höchli
M
M
Altwegg
M
M
Schaffner
A
A
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
D003470:Culture Media; D016753:Interleukin-10; D015847:Interleukin-4; D003907:Dexamethasone