STRAIN VARIATION IN PATHOGENESIS AND IMMUNITY IN GIARDIA INFECTION
Singer, Steven M
Infection with Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis) is one of the most common intestinal protozoan infections in humans all around the world. Symptoms associated with human giardiasis are diverse an iinfected patients may develop abdominal cramps, nausea, and acute/subacute or chronic diarrhea, accompanied with malabsorptionsyndrome. Transmission of the parasite to a new host happens via the ingestion of cyst contaminated food and water. Human infections with G. duodenalis are distributed worldwide with rates of infections between 2-5% in developed nations and 20-30% in the developing world.Several reports have demonstrated variations in symptoms/ pathology among different Giardia isolates. There is evidence supporting that a specific genotype of G. duodenalis (i.e. assemblage A or B) is associated with symptomatic disease. These reports are sometimes contradictory. Forexample, it was shown that 74% of isolates examined from symptomatic patients in Nepal were assemblage B while 20% and 6% were assemblage A and mixed infections, respectively. In contrast, others showed assemblage A to be predominantly associated with symptomatic diseasein Bangladesh. However, some reports do not find any correlation between the parasite genotype and symptomatic disease. In order to evaluate the strain-dependent variability among the two assemblages capable of infecting humans, we used representative strains of both assemblages to infect mice. We then comparatively analyzed immune responses to the two stain of the parasite. Analyses showed that there were strain-dependent differences in the ability of a given strain to induce pathological changes.Using a mouse model of giardiasis, we examined the role of host immunity and pathogen virulence in mediating disaccharidase deficiency postinfection. 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. β2-Microglobulin knockout animals controlled infections similar to wild-type mice but exhibited no decrease in disaccharidase activity. Analysis of cytokine production by spleenand mesenteric lymph node cells showed production of IL-4, IL-10, IL-13, IL-17, IL-22, TNF-α, and IFN-γ post-infection with both WB and GS, with IFN-g being the dominant cytokine for both strains.It has recently been hypothesized that most pathology induced during human giardiasis is, in fact, because of the immune responses meant to eliminate the parasites. The structural proteins ezrin and villin are among the most abundant proteins present in the intestinal brush border. These proteins function as cross-linkers between the plasma membrane and the actin cytoskeleton. We found that intestinal epithelial cells (IECs) underwent drastic cytoskeletal changes following gut infection and that both expression and the distribution of the cytoskeletal proteins were impacted by gut infection. We further demonstrated that the immense changes observed following gut infections are driven by host adaptive immunity, and that the lack of adaptive immune responses prevents hosts from exhibiting these changes. We also showed a correlation between tyrosine-phosphorylation of villin and the presence of disaccharidase deficiency in mice infected with the two strains of the parasite.
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Giardia lamblia, the Intestinal Microbiome, and Innate Immunity: A Study of the Host-Parasite Relationship during G. lamblia Infection Maloney, Jenny G. (Georgetown University, 2015)Infection with the protozoan parasite G. lamblia is a major cause of diarrheal disease worldwide. Prevalence is highest in developing countries with an estimated 20-30% of the population infected at any given time. G. ...