Jejunal brush border microvillous alterations in Giardia muris-infected mice: Role of T lymphocytes and interleukin-6

Intestinal colonization with the protozoan Giardia causes diffuse brush bor der microvillous alterations and disaccharidase deficiencies, which in turn are responsible for intestinal malabsorption and maldigestion. The role of T cells and/or cytokines in the pathogenesis of Giardin-induced microvillo us injury remains unclear, The aim of this study was to assess the role of T tells and interleukin-6 (IL-6) in the brush border pathophysiology of acu te murine giardiasis in vivo. Athymic nude (nu(-)/nu(-)) CD-1 mice and isog enic immunocompetent (nu(+)/nu(+)) CD-1 mice (4 weeks old) received an axen ic Giardia muris trophozoite inoculum or vehicle (control) via orogastric g avage, Weight gain and food intake were assessed daily. On day 6, segments of jejunum were assessed for parasite load, brush border ultrastructure, IL -6 content, maltase and sucrase activities, villus-crypt architecture, and intraepithelial lymphocyte (IEL) infiltration. Despite similar parasitic lo ads on day 6, infected immunocompetent animals, but not infected nude mice, showed a diffuse loss of brush border microvillous surface area, which was correlated with a significant reduction in maltase and sucrase activities and a decrease in jejunal IL-6 concentration. In both athymic control and i nfected mice,jejunal brush border surface area and disaccharidases were hig h, but levels of tissue IL-6 were low and comparable to the concentration m easured in immunocompetent infested animals. In both immunocompetent and nu de mice, infection caused a small but significant increase in the numbers o f IELs. These findings suggest that the enterocyte brush border injury and malfunction seen in giardiasis is, at least in part, mediated by thymus-der ived T lymphocytes and that suppressed jejunal IL-6 does not necessarily ac company microvillous shortening.