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Infection and Immunity, June 2000, p. 3412-3418, Vol. 68, No. 6
Department of Biological Sciences, University
of Calgary, Calgary, Alberta, Canada T2N 1N4
Received 21 October 1999/Returned for modification 10 January
2000/Accepted 24 March 2000
Intestinal colonization with the protozoan Giardia
causes diffuse brush border 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 Giardia-induced microvillous injury
remains unclear. The aim of this study was to assess the role of T
cells and interleukin-6 (IL-6) in the brush border pathophysiology of
acute murine giardiasis in vivo. Athymic nude
(nu
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Jejunal Brush Border Microvillous Alterations in
Giardia muris-Infected Mice: Role of T Lymphocytes and
Interleukin-6
/nu
) CD-1 mice and isogenic
immunocompetent (nu+/nu+) CD-1 mice (4 weeks
old) received an axenic Giardia muris trophozoite inoculum
or vehicle (control) via orogastric gavage. 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 loads 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 infected mice, jejunal brush border surface
area and disaccharidases were high, but levels of tissue IL-6 were low
and comparable to the concentration measured in immunocompetent
infected animals. In both immunocompetent and nude mice, infection
caused a small but significant increase in the numbers of IELs. These
findings suggest that the enterocyte brush border injury and
malfunction seen in giardiasis is, at least in part, mediated by
thymus-derived T lymphocytes and that suppressed jejunal IL-6 does not
necessarily accompany microvillous shortening.
*
Corresponding author. Mailing address: 2500 University
Dr. N.W., Calgary, Alberta, Canada T2N 1N4. Phone: (403) 220-2817. Fax:
(403) 289-9311. E-mail: aburet{at}ucalgary.ca.
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