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

Protease-activated receptor 2 ( PAR(2)) is a cell surface receptor that detects trypsin and trypsin-like enzymes. Although the precise pathophysiological roles of PAR(2) are yet to be determined, the receptor has been broadly implicated in inflammation and allergy. However, no studies have investigated the possible roles of PAR(2) in hosts infected by parasitic helminths. Therefore, in this preliminary investigation, we compared the infectivity of the nematode Nippostrongylus brasiliensis in mice lacking the PAR(2) gene (PAR(2)(-/-)) and in their `background-strain' controls ( 129SV). PAR(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 PAR(2)-activating peptide SLIGRL (single letter amino acid sequence) but not the inactive reverse peptide LRGILS. These findings provide initial support for the proposal that PAR(2) is a recognition receptor for nematode-derived proteases.