The role of arginine in intestinal infection.

Abstract

<p>An overview of the intestinal epithelial lining is given in B, with a villus and a crypt being depicted. Proliferating cells in the crypts migrate towards the tip of the villus, undergoing differentiation, and are shed at the tip of the villus after cell death. <i>Giardia</i> trophozoites sit all along the epithelial surface (with exception of the Paneth cells that are most down in the crypts) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045325#pone.0045325-Aley1" target="_blank">[47]</a>. A trophozoite attached to an IEC is shown in A. Dotted lines indicate molelcules released by the trophozoite. Arginine is actively taken up by the parasite and converted into CO₂, NH₃ and ornithine along the dihydrolase pathway, indicated by the enzymes ADI (arginine deiminase), OCT (ornithine carbamoyl transferase) and CK (carbamate kinase). Ornithine is released via an arginine-ornithine antiporter, blocks the cationic amino acid transporters (CAT) of IECs and thereby uptake of arginine. In addition, arginine is degraded extracellular by ADI and OCT released from <i>Giardia</i> upon interaction. All this leads to reduced arginine availability within the host IEC. As shown within this study, the consequences are reduced polyamine levels in IECs that result in cell cycle arrest via upregulation of cell cycle block genes (GADD45A, BTG3). This reduced cell proliferation in the crypts could lower intestinal cell turnover and reduce cell differentiation along the villus-axis, allowing the parasite to live in a more stable environment. The reduced arginine availability in IECs also leads to decreased production of the antimicrobial agent nitric oxide (NO) via nitric oxide synthases (NOS) in all cells of the intestinal epithelial lining.</p