Initial support for the hypothesis that PAR2 is involved in the immune response to Nippostrongylus brasiliensis in mice

Protease-activated receptor 2 (PAR₂) is a cell surface receptor that detects trypsin and trypsin-like enzymes. Although the precise pathophysiological roles of PAR₂ are yet to be determined, the receptor has been broadly implicated in inflammation and allergy. However, no studies have investigated the possible roles of PAR₂ in hosts infected by parasitic helminths. Therefore, in this preliminary investigation, we compared the infectivity of the nematode Nippostrongylus brasiliensis in mice lacking the PAR₂ gene ${\left( {{\text{PAR}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-0em} - }}_{2} } \right)}$ and in their ‘background-strain’ controls (129SV). ${\text{PAR}}^{{ - \mathord{\left/ {\vphantom { - - }} \right. \kern-0em} - }}_{2} $ mice displayed elevated fecal egg counts and decreased levels of total serum IgE, after a subcutaneous infection with 900 infective third-stage N. brasiliensis larvae compared with 129SV mice that were not susceptible to infection. In addition, in a separate study in BALB/c mice, two immunological hallmarks of parasite infection, IgE- and IL-10-expressing lymphocytes, were shown to be augmented after the coadministration of the classic antigen ovalbumin with the PAR₂-activating peptide SLIGRL (single letter amino acid sequence) but not the inactive reverse peptide LRGILS. These findings provide initial support for the proposal that PAR₂ is a recognition receptor for nematode-derived proteases.