title: Host immunity and pathogen strain contribute to intestinal disaccharidase impairment following gut infection.
abstract: Infection or other inflammatory insults in the small intestine often result in reduced disaccharidase enzyme levels. Using a mouse model of giardiasis, we examined the role of host immunity and pathogen virulence in mediating disaccharidase deficiency postinfection (p.i.). C57BL/6J mice were infected with two strains, WB and GS, of the human parasite Giardia duodenalis. The levels of sucrase, maltase, and lactase decreased in wild-type mice p.i. with the GS strain but not with the WB strain. Both CD4-deficient and SCID mice failed to eliminate the infection and did not exhibit disaccharidase deficiency. β(2)-Microglobulin knockout animals controlled infections similar to wild-type mice but exhibited no decrease in disaccharidase activity. Analysis of cytokine production by spleen and mesenteric lymph node cells showed production of IL-4, IL-10, IL-13, IL-17, IL-22, TNF-α, and IFN-γ p.i. with both WB and GS, with IFN-γ being the dominant cytokine for both parasite strains. Mesenteric lymph node cells produced lower levels of cytokines compared with splenocytes in response to parasite extract, although the overall pattern was similar. These data suggest that T cell responses mediate parasite clearance whereas also contributing to pathogenesis. They also demonstrate that differences in pathogen strain can also determine the outcome of infection and further our understanding of the clinical variation seen in human giardiasis.
authors.affiliation: Department of Biology, Georgetown University, Washington, DC 20057, USA.
authors.forename: Shahram
authors.initials: S
authors.lastname: Solaymani-Mohammadi
authors.forename: Steven M
authors.initials: SM
authors.lastname: Singer
mesh_terms: D000818:Animals; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004186:Disaccharidases / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D016829:Giardia lamblia / Q000235:genetics / Q000276:immunology; D005873:Giardiasis / Q000201:enzymology* / Q000276:immunology / Q000469:parasitology*; D007421:Intestine, Small / Q000201:enzymology / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D004186:Disaccharidases