ARRTI Speaker Series - 2014

December 9, 2014

Dr. Staffan Svärd

Uppsala University
Department of Cell and Molecular Biology
Uppsala, Sweden

"Host-parasite interactions during Giardia infections"

G. intestinalis (synonymous with Giardia lamblia and Giardia duodenalis) is one of the most common parasitic infections worldwide. It contributes to an estimated 280 million symptomatic human infections (giardiasis) per year and since 2004, has been included as part of the WHO Neglected Disease Initiative. Giardia is a potential zoonosisandinfection in young farm animalscan have an economical impact due to loss in productivity. However, there is relatively little insight into how Giardia causes disease; it is not invasive and secretes no known toxin.

We have studied host parasite interactions in an in vitro system that mimics the intestinal environment. RNA sequencing and proteomics was performed on human intestinal epithelial cells (Caco2) and parasites. We could detect strong responses in human intestinal epithelial cells after 1.5 hours, dropping at later time points of 3 and 4.5 hours. Gene network analysis revealed that Giardia-infection leads to the immediate activation of chemokines (CCL2, CCL20, CXCL1, CXCL2, CXCL3) and cytokines (IL8) on the RNA level but the level of secreted cytokines is low. Further, regulatory proteins of apoptosis and proliferation as well as cell adhesion molecules were induced after 1.5 hours of host-parasite interaction. Most of the early induced genes were down-regulated on transcript-level before 3 hours. Data analysis suggested that this was due to RNA decay of AU-rich element-containing transcripts. In the parasites the expression of high-cysteine rich membrane proteins and genes related to protection against oxidative stress was induced.

When parasites were exposed to conditions mimicking the lower intestinal tract the parasites differentiated to the infective cyst stage. This differentiation was studied using RNA Seq and epitope tagging. Only 13 of the around 6000 G. intestinalis protein encoding genes are consistently up regulated early during encystation. We also detected a switch of variant specific surface proteins (VSPs) in the late phase of encystation. This occurred at the same time as nuclear division and DNA replication, suggesting a potential link between the processes.

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