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Infection and Immunity, December 2001, p. 7380-7386, Vol. 69, No. 12
Department of Parasitology and Immunology,
The University of Tokushima School of Medicine, Tokushima, Japan
Received 31 May 2001/Returned for modification 6 August
2001/Accepted 7 September 2001
During infection, parasites evade the host immune system by
modulating or exploiting the immune system; e.g., they suppress expression of major histocompatibility 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. In this study, we identified a new cysteine protease inhibitor, nippocystatin, derived from excretory-secretory (ES) products of an intestinal nematode, Nippostrongylus brasiliensis. Nippocystatin, which belongs
to cystatin family 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 nippocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of splenocytes but not non-antigen-specific proliferation of splenocytes. OVA-specific cytokine production was also
greatly suppressed in rNbCys-treated mice. Although the serum levels of
both OVA-specific immunoglobulin G1 (IgG1) and IgG2a were not affected
by rNbCys treatment, OVA-specific IgE was preferentially downregulated
in rNbCys-treated mice. In vitro rNbCys inhibited processing of OVA by
lysosomal cysteine proteases from the spleens of mice. Mice with
anti-nippocystatin antibodies became partially resistant to infection
with N. brasiliensis. Based on these findings, N. brasiliensis appears to skillfully evade host immune systems by
secreting nippocystatin, which modulates antigen processing in
antigen-presenting cells of hosts.
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.12.7380-7386.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Nippocystatin, a Cysteine Protease Inhibitor from
Nippostrongylus brasiliensis, Inhibits Antigen Processing
and Modulates Antigen-Specific Immune Response
*
Corresponding author. Mailing address:
Department of Dermatology, Graduate School of Medical Sciences, Kyushu
University, Fukuoka 812-8582, Japan. Phone: 81-92-642-5585. Fax:
81-92-642-5600. E-mail:
dainichi{at}dermatol.med.kyushu-u.ac.jp.
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