Abstract
The T-cell-mediated immune response exhibits a crucial function in the control of the intrahepatic proliferation of Echinococcus multilocularis larvae in mice and humans, both being natural intermediate hosts of the parasite. Antigen B ( AgB), a metabolized Echinococcus spp. lipoprotein, contributes to the modulation of the T-cell immune response, and distinct sites of the corresponding AgB1, AgB3 and AgB4 genes were shown to be under positive selection pressure. Since several AgB gene variants are present in a single Echinococcus metacestode, we used secondary E. multilocularis infections in BALB/c and in athymic nude mice (devoid of T-cell responses) to analyze the effect of the cellular immune response on the expression and diversity of EmAgB1– EmAgB4 genes. We demonstrated hereby that EmAgB transcripts were less abundant in nude mice during the early phase of infection (at one month post-infection), and that EmAgB2 is simultaneously down-regulated when compared to the other three genes. A negative relationship exists between the level of transcription and diversity of EmAgB genes. Moreover, no excess of non-synonymous substitutions was found among the distinct EmAgB alleles from a single host. Together, these results pointed to the effect of purifying selection, which seemed to eliminate the detrimental AgB variants generated during the development of the metacestode within the peritoneal cavity of its intermediate host.
Highlights
IntroductionDepartamento de Genética, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500 Prédio 43323, Caixa Postal 15053, Porto Alegre, RS, CEP 91501-970, Brazil
In order to determine the evolutionary significance of EmAgB diversity inside a single E. multilocularis metacestode, we looked for evidences of natural selection on transcript variability
We quantified the transcription of EmAgB1–EmAgB4, hereby reporting that the Antigen B (AgB) mutations originated in both mouse strains during parasite development
Summary
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500 Prédio 43323, Caixa Postal 15053, Porto Alegre, RS, CEP 91501-970, Brazil. Alveolar echinococcosis is a severe human life-threatening zoonosis caused by the infection with the larval stage of the fox tapeworm Echinococcus multilocularis. It is characterized by the growth of a tumor-like larval tissue, the so-called metacestode, which primarily infiltrates the host target organ (liver) and secondarily may form metastases in other organs or sites. Because of the growth behavior and the potential of the E. multilocularis metacestode to form metastases, alveolar echinococcosis is considered the most lethal helminthic infection in humans (Craig et al, 1996).
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