title: Echinococcus multilocularis proliferation in mice and respective parasite 14-3-3 gene expression is mainly controlled by an alphabeta CD4 T-cell-mediated immune response.
abstract: The role of specific B lymphocytes and T-cell populations in the control of experimental Echinococus multilocularis infection was studied in micro MT, nude, T-cell receptor (TCR)-beta(-/-), major histocompatibility complex (MHC)-I(-/-) and MHC-II(-/-) mice. At 2 months postinfection, the parasite mass was more than 10 times higher in nude, TCR-beta(-/-) and MHC-II(-/-) mice than in infected C57BL/6 wild-type (WT) mice, and these T-cell-deficient mice started to die of the high parasite load at this time-point. In contrast, MHC-I(-/-) and micro MT mice exhibited parasite growth rates similar to those found in WT controls. These findings clearly point to the major role that CD4(+) alphabeta(+) T cells play in limiting the E. multilocularis proliferation, while CD8(+) T and B cells appeared to play a minor role in the control of parasite growth. In the absence of T cells, especially CD4(+) or alphabeta(+) T cells, the cellular immune response to infection was impaired, as documented by the lack of hepatic granuloma formation around the parasite and by a decreased splenocyte responsiveness to concanavalin A (Con A) and parasite antigen stimulation. Surprisingly, in T-cell-deficient mice, the ex vivo expression of interferon-gamma (IFN-gamma) and other inflammatory cytokines (except for interleukin-6) were increased in association with a high parasite load. Thus, the relative protection mediated by CD4(+) alphabeta(+) T cells against E. multilocularis infection seemed not be IFN-gamma dependent, but rather to rely on the effector's function of CD4(+) alphabeta(+) T cells. The local restriction of parasite germinal cell proliferation was reflected by a regulatory effect on the expression of 14-3-3 protein within the parasite tissue in T-cell-deficient mice. These results provide a strong indication that the CD4(+) alphabeta(+) T-cell-mediated immune response contributes to the control of the parasite growth and to the regulation of production of the parasite 14-3-3 protein in metacestode tissues.
authors.affiliation: Institute of Parasitology, University of Berne, Berne, Switzerland.
authors.forename: Wen Juan
authors.initials: WJ
authors.lastname: Dai
authors.forename: Andreas
authors.initials: A
authors.lastname: Waldvogel
authors.forename: Mar
authors.initials: M
authors.lastname: Siles-Lucas
authors.forename: Bruno
authors.initials: B
authors.lastname: Gottstein
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D004443:Echinococcosis / Q000276:immunology*; D004446:Echinococcus / Q000235:genetics; D015870:Gene Expression; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D048948:14-3-3 Proteins; D000941:Antigens; D016207:Cytokines; D003208:Concanavalin A; D014446:Tyrosine 3-Monooxygenase