Echinococcus multilocularis proliferation in mice and respective parasite 14-3-3 gene expression is mainly controlled by an αβ+ CD4+ T-cell-mediated immune response

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Abstract

SUMMARY

The role of specific B lymphocytes and T-cell populations in the control of experimental Echinococus multilocularis infection was studied in μMT, nude, T-cell receptor (TCR)-β−/−, 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-β−/− 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 μMT mice exhibited parasite growth rates similar to those found in WT controls. These findings clearly point to the major role that CD4+ αβ+ 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 αβ+ 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-γ (IFN-γ) and other inflammatory cytokines (except for interleukin-6) were increased in association with a high parasite load. Thus, the relative protection mediated by CD4+ αβ+ T cells against E. multilocularis infection seemed not be IFN-γ dependent, but rather to rely on the effector's function of CD4+ αβ+ 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+ αβ+ 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.

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