RNA expression changes of arginine-consuming enzymes upon Giardia-host cell interaction. Based on an interpretation of results from this and previous studies, the encircled numbers point out various ways by which Giardia interferes with the host immune response: (1) consumption of arginine via arginine-ornithine antiporter, (2) release of arginine-consuming ADI and OCT, (3) blocking of arginine-uptake into host cells by ornithine, (4) down-regulation of host iNOS, (5) up-regulation of host ODC, (6) up-regulation of parasite FlHb upon NO-stress. Human intestinal epithelial cells (Caco-2) were in vitro interacted with Giardia trophozoites and the expression changes of arginine-consuming enzymes were assessed by qPCR. Various enzymes involved in the arginine-metabolism of host cells and of Giardia are shown (adapted from Stadelmann et al 2012 ). Changes in expression after 1.5, 3, 6 and 24 h as compared to 0 h are indicated for interactions with the parasite isolate WB according to Figures 2 and 4 (square for no change, triangle pointing up for up-regulation, triangle pointing down for down-regulation; cut-off value 2). Expression of inos and flhb in host cells that were stimulated with cytokines (TNF-α (200 ng/mL), IL-1α (200 ng/mL), IFN-γ (500 ng/mL) to produce nitric oxide is also shown (non-filled triangles for up- and down-regulation, non-filled square for no change). ADC, arginine decarboxylase; ADI, arginine deiminase; AGAT, arginine-glycine amidinotransferase; ARG, arginase; ASL, argininosuccinate lyase; ASS, argininosuccinate synthetase; CAT, cationic amino acid transporter; CK, carbamate kinase; FlHb, flavohemoglobin; NO, nitric oxide; NOS, nitric oxide synthase; OAT, ornithine aminotransferase; OCT, ornithine carbamoyl transferase; ODC, ornithine decarboxylase; p6C, Δ1-pyrroline-5-carboxylate.
Stadelmann et al. BMC Microbiology 2013 13:256 doi:10.1186/1471-2180-13-256