Project: Parasitic nematodes modulate common protease-based activation of host innate immunity in plants and animals

Parasitic nematodes are a major threat to plant, animal and human health. A common characteristic of plant- and animal-parasitic nematodes is their phenomenal persistence inside the host, presumably resulting from their ability to suppress host immunity.

However, the mechanisms of immunomodulation by parasitic nematodes in plants and animals are not well understood. It is thought that secretions released by parasitic nematodes are instrumental in the persistence of infections in both plants and animals. Recently, we have shown that a secreted venom-allergen-like protein of a plant-parasitic nematode inhibits an extracellular cysteine protease that acts as a signalling node in innate immunity of tomato plants. Venom allergen-like proteins are abundantly secreted by all parasitic nematodes, but the role of these proteins in parasitism has thus far remained elusive. Our data further demonstrates that venom allergen-like proteins from both plant- and animal-parasitic nematodes suppress the beta-glycan-induced pro-inflammatory response in human macrophages, suggesting that they target common pathways in innate immunity of plants and animals.

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These beta-glycans are recognised by extracellular pattern-recognition receptors on the surface of immune cells. We therefore hypothesize that parasitic nematodes modulate the activation of pattern-recognition receptors via extracellular cysteine proteases in both plants and animals. The objective of this proposal is to elucidate the role of the abundantly secreted venom-allergen-like proteins in suppressing or evading immune responses in both plants and animals. The knowledge arising from this project will enable plant breeding companies and pharmaceutical companies to develop novel nematode resistant food crops and novel anthelmintic treatments for livestock.