This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dainichi, T.
Right arrow Articles by Himeno, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dainichi, T.
Right arrow Articles by Himeno, K.

 Previous Article  |  Next Article 

Infection and Immunity, December 2001, p. 7380-7386, Vol. 69, No. 12
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

Teruki Dainichi,* Yoichi Maekawa, Kazunari Ishii, Tianqian Zhang, Baher Fawzy Nashed, Tohru Sakai, Miwa Takashima, and Kunisuke Himeno

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.


* 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.


Infection and Immunity, December 2001, p. 7380-7386, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7380-7386.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Ford, L., Guiliano, D. B., Oksov, Y., Debnath, A. K., Liu, J., Williams, S. A., Blaxter, M. L., Lustigman, S. (2005). Characterization of a Novel Filarial Serine Protease Inhibitor, Ov-SPI-1, from Onchocerca volvulus, with Potential Multifunctional Roles during Development of the Parasite. J. Biol. Chem. 280: 40845-40856 [Abstract] [Full Text]  
  • Diez-Tascon, C., Keane, O. M., Wilson, T., Zadissa, A., Hyndman, D. L., Baird, D. B., McEwan, J. C., Crawford, A. M. (2005). Microarray analysis of selection lines from outbred populations to identify genes involved with nematode parasite resistance in sheep. Physiol. Genomics 21: 59-69 [Abstract] [Full Text]  
  • Schierack, P., Lucius, R., Sonnenburg, B., Schilling, K., Hartmann, S. (2003). Parasite-Specific Immunomodulatory Functions of Filarial Cystatin. Infect. Immun. 71: 2422-2429 [Abstract] [Full Text]  
  • Dickinson, D.P. (2002). SALIVARY (SD-TYPE) CYSTATINS: OVER ONE BILLION YEARS IN THE MAKING--BUT TO WHAT PURPOSE?. CROBM 13: 485-508 [Abstract] [Full Text]  
  • Valenzuela, J. G., Francischetti, I. M. B., Pham, V. M., Garfield, M. K., Mather, T. N., Ribeiro, J. M. C. (2002). Exploring the sialome of the tick Ixodes scapularis. J. Exp. Biol. 205: 2843-2864 [Abstract] [Full Text]