What is the role of epithelial barrier dysfunction in the pathogenesis of giardiasis?

Updated: Oct 01, 2018
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: Burt Cagir, MD, FACS  more...
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Epithelial barrier dysfunction in cases with chronic giardiasis is associated with increased rates of enterocyte apoptosis. Consistent with these observations, microarray analyses of the effects of G intestinalis on human CaCo2 cells found that the parasite–host interactions lead to a pronounced up-regulation of genes implicated in the apoptotic cascade and the formation of reactive oxygen species.

Panaro et al demonstrated that Giardia trophozoites induce cell apoptosis by activation of both intrinsic and extrinsic apoptotic pathways, down-regulation of the antiapoptotic protein Bcl-2, and up-regulation of the proapoptotic Bax. These findings suggest a possible role for caspase-dependent apoptosis in the pathogenesis of giardiasis. [28]

Giardia can also prevent the formation of nitric oxide, a compound known to inhibit giardial growth, by consuming local arginine, which effectively removes the substrate needed by enterocytes to produce nitric oxide. This mechanism may contribute to Giardia -induced enterocyte apoptosis because arginine starvation in these cells is known to cause programmed cell death. [19, 29]

G intestinalis is genetically heterogeneous with 8 genetically distinct genotypes or assemblages, designated A-H; assemblages A and B can infect humans. Genotypes vary within group A and B, which could explain why the role of animals in the epidemiology of human infection remains poorly understood. [30, 31] Some strains appear more biologically suitable than other strains. This feature is potentially important in giardiasis pathogenesis. [32, 33] Genotypically diverse isolates of Giardia species may vary in their ability to produce morphologic changes in the small intestine epithelium and to impair fluid, electrolyte, and solute transport. [34]

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