Host immunity and pathogen genotype contribute to disaccharidase impairment following gut infection in vivo (99.23)

Abstract

Abstract Using a mouse model of infection with the GS strain of the human parasite Giardia duodenalis, we examined the role of host immunity and pathogen genotype in inducing disaccharidase deficiency. The levels of sucrase, maltase, and lactase decreased in the small intestines of C57BL/6J mice at the peak of infection. Lack of functional adaptive immunity in SCID mice resulted in increased parasite burdens, failure to eliminate the infection and no impairment of intestinal enzymes. Experiments using beta2microglonbulin knockout animals implicated CD8+ T cells as mediating disaccharidase deficiency. Interestingly, wild-type mice infected with the WB strain of G. duodenalis, did not exhibit decreased disaccharidase levels. These strains are prototypes of two genetically distinct assemblages within the species G. duodenalis, suggesting that the assemblages may be distinct in causing disaccharidase deficiency in human infections. Analysis of in vitro cytokine production by CD4+ T cells in response to pathogen extracts showed similar production of IL-4, IL-10, IL-13, IL-22, TNF-alpha and IFN-gamma following infection with IFN-gamma being the dominant cytokine for both parasite strains. These findings reveal the significance of both host and pathogen factors as key players in determining the outcome of murine infections, and may explain why some human patients exhibit malnutrition syndrome while others do not.