Helminths
are masterful manipulators of the immune system, a strategy that promotes their
long-term survival. Epidemiological and clinical studies have shown that parasitic
infections condition the immune system to prevent inappropriate immune
responses, a phenomenon that is embodied by the hygiene hypothesis. Much of the
immunoregulatory prowess of helminths can be attributed to the secretion into
host tissues of a suite of compounds that modulate immune responses. Identification of these immunomodulatory
components is driven by the need to develop novel therapies, preferably of low
molecular weight, for chronic inflammatory diseases with limited treatment
options. Here, we use a RP-HPLC and LC-MS/MS approach to isolate therapeutic
compounds from hookworm excretory/secretory (ES) products with a molecular
weight below 10 kDa. Therapeutic activity was tested in a chemically induced
model of colitis (TNBS), which revealed a fraction that protected mice from weight
loss and colon inflammation. Further purification is underway to identify and
structurally characterise the specific molecule, with a view to synthesising
novel helminth-derived biologics for treating chronic inflammatory conditions.