title: Echinococcus multilocularis: inflammatory and regulatory chemokine responses in patients with progressive, stable and cured alveolar echinococcosis.
abstract: The progressive growth of Echinococcus multilocularis metacestodes and their tissue infiltration will cause organ malfunction and finally failure. In few patients, E. multilocularis metacestode proliferation will spontaneously regress, but little is known about the determinants which may restrain metacestode survival and growth. In this study, chemokine responses were investigated in E. multilocularis patients at different states of infection, i.e. with progressive, stable and cured alveolar echinococcosis (AE). Characteristic chemokine profiles and changes in their production were observed in AE patients and infection-free controls when their peripheral blood cells were cultured with E. multilocularis antigens. The production of CC and CXC chemokines which associate with inflammation (MIP-1 alpha/CCL3, MIP-1 beta/CCL4, RANTES/CCL5 and GRO-alpha/CXCL1) was constitutively larger in AE patients than in controls; and the elevated chemokine releases were equal in patients with progressive, stable or cured AE. Cluster analyses identified three distinct chemokine response profiles; chemokines were enhanced, depressed or produced in similar quantities in AE patients and controls. A disparate cellular responsiveness was observed in AE patients to viable E. multilocularis vesicles; cluster 1 (GRO-alpha/CXCL1, MCP-3/CCL7, MCP-4/CCL13, TARC/CCL17, LARC/CCL20) and cluster 2 chemokines (PARC/CCL18, MDC/CCL22, MIG/CXCL9) were clearly diminished, while cluster 3 chemokines (MIP-1 alpha/CCL3, MIP-1 beta/CCL4, RANTES/CCL5) augmented. The increased production of inflammatory chemokines in patients even with cured AE could be induced by residual E. multilocularis metacestode lesions which continuously stimulate production of inflammatory chemokines. E. multilocularis metacestodes also suppressed cellular chemokine production in AE patients, and this may constitute an immune escape mechanism which reduces inflammatory host responses, prevents tissue destruction and organ damage, but may also facilitate parasite persistence.
authors.affiliation: Institute for Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Kocherscheidt
authors.affiliation: Institute for Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany.
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Flakowski
authors.affiliation: Section of Infectious Diseases and Clinical Immunology, University of Ulm, Robert-Koch-Straße 8, 89081 Ulm, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Grüner
authors.affiliation: Institute for Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Hamm
authors.affiliation: Department of Medical Biometry, University of Tübingen, Westbahnhofstraße 55, 72070 Tübingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietz
authors.affiliation: Section of Infectious Diseases and Clinical Immunology, University of Ulm, Robert-Koch-Straße 8, 89081 Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kern
authors.affiliation: Institute for Tropical Medicine, University of Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Soboslay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D018925:Chemokines / Q000096:biosynthesis* / Q000145:classification; D016000:Cluster Analysis; D004444:Echinococcosis, Hepatic / Q000276:immunology* / Q000473:pathology; D048210:Echinococcus multilocularis / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D018925:Chemokines