T. Dainichi et al., Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response, INFEC IMMUN, 69(12), 2001, pp. 7380-7386
During infection, parasites evade the host immune system by modulating or e
xploiting the immune system; e.g., they suppress expression of major histoc
ompatibility complex class II molecules or secrete cytokine-like molecules.
However, it is not clear whether helminths disturb the immune responses of
their hosts by controlling the antigen-processing pathways of the hosts. I
n this study, we identified a new cysteine protease inhibitor, nippocystati
n, derived from excretory-secretory (ES) products of an intestinal nematode
, Nippostrongylus brasiliensis. Nippocystatin, which belongs to cystatin fa
mily 2, consists of 144 amino acids and is secreted as a 14-kDa mature form
. In vivo treatment of ovalbumin (OVA)-immunized mice with recombinant nipp
ocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of sple
nocytes but not non-antigenspecific proliferation of splenocytes. OVA-speci
fic cytokine production was also greatly suppressed in rNbCys-treated mice.
Although the serum levels of both OVA-specific immunoglobulin G1 (IgG1) an
d IgG2a were not affected by rNbCys treatment, OVA-specific IgE was prefere
ntially downregulated in rNbCys-treated mice. In vitro rNbCys inhibited pro
cessing of OVA by lysosomal cysteine proteases from the spleens of mice. Mi
ce with anti-nippocystatin antibodies became partially resistant to infecti
on with N. brasiliensis. Based on these findings, N. brasiliensis appears t
o skillfully evade host immune systems by secreting nippocystatin, which mo
dulates antigen processing in antigen-presenting cells of hosts.