Pathogenicity and virulence of Giardia intestinalis.

Giardiasis, caused by Giardia intestinalis, is a prevalent intestinal protozoan infection worldwide. Clinical manifestations are variable, and many infections remain asymptomatic. Disease pathogenesis is multifactorial, involving brush border enzyme deficiency, apoptosis, dysbiosis and increased intestinal permeability. Advances in genomics, genetic tools, and model systems have substantially improved our understanding of the parasite's virulence mechanisms. Giardia exhibits considerable genetic diversity, with distinct assemblages associated with differences in parasite biology. Attachment is mediated by the ventral disk, while the parasite's eight flagella contribute to motility and intestinal persistence. Antigenic variation of cysteine-rich surface proteins enables immune evasion and promotes chronic infection but the level of inflammation is low. The parasite releases a variety of proteins and extracellular vesicles containing proteins and small RNAs that play important roles in host-cell interactions and modulation of the gut microbiome. This review describes areas that need further research to connect pathogenesis to specific virulence mechanisms.