Proteases in helminth- and allergen- induced inflammatory responses

Abstract

Proteolytic activity is a central biochemical property that endows molecules with intrinsic allergenicity. Thus, the cysteine protease of dust mite, Der p1, the aspartic protease of cockroach, Bla g 2, the serine protease of Aspergillus fumigatus and the bacterial subtilisins are all major allergenic molecules responsible for the increase in asthma and atopic conditions worldwide. These proteases induce Th2-driven inflammatory responses in the airways by disrupting the epithelial cell junctions so that these, and other molecules, gain access to, and alter the function of, underlying cells of the innate immune system (dendritic cells, mast cells, basophils and macrophages) and B and T cells. Helminth parasites secrete proteases to gain entry into their hosts, and to feed on and migrate through tissues. Their action leads to tissue damage and the activation of inflammatory responses dominated by elevated IgE, eosinophilia and Th2 cells, much like allergenic responses. In certain situations, such as in acute infections (especially with zoonotic helminths), proteases secreted by helminths may sensitise individuals to allergens. However, the anti-inflammatory responses observed in chronic helminthiases, involving IL-10 and TGFBeta, that are primarily responsible for controlling immune-mediated damage to the host that is initiated by secreted proteases, coincidentally protects against similar inflammatory damage by allergens.