Abstract
Innate Immunity, Volume 24 Issue 7, October 2018
The elucidation of the structure–function relation of compounds isolated from natural sources often suffers from lack of purity. It is still true to say, “Don’t spend clean thinking on dirty substances!” A recent example is Gram-positive bacterial lipoteichoic acid (LTA) which was (and still is in many publications) published to represent an agonist of TLR2. Chemically synthesized pure LTA proved that this is not the case and that, instead, contaminating lipopeptides are the active molecules. Another example, but with a different outcome, is the lipid A of Gram-negative bacterial lipopolysaccharide (LPS) that had been proposed since the 1950s to represent the endotoxic principle. Several immunologists doubted that, and argued instead that some other components present in minor amounts could be responsible for the endotoxic activity. This discussion was ceased in the mid-1980s after lipid A had been synthesized chemically at the highest purity, and when this compound showed the very same endotoxic activity as lipid A isolated from Escherichia coli, proving that no contaminations were responsible for its agonistic properties.
In this important paper, Tombácz et al. report on Toxoplasma gondii profilin (TgPr) – a protein integral to parasite movement and cellular invasion. Murine TLRs had been described to bind TgPr, and the finding that human TLR5 recognize recombinant TgPr had been published. However, as now shown by Tombácz et al., human and bovine TLR5-transfected cells do not respond to profilin, and TgPr does not stimulate IL-6 secretion in human peripheral blood mononuclear cells and CD14 monocytes. Their data indicate that TgPr may not be a ligand for TLR5, and that the response described earlier could have originated from impurities in the profilin preparation.