Back to Search
Start Over
Modulation of goat monocyte function by HCcyst-2, a secreted cystatin from Haemonchus contortus.
- Source :
-
Oncotarget [Oncotarget] 2017 Jul 04; Vol. 8 (27), pp. 44108-44120. - Publication Year :
- 2017
-
Abstract
- Modulation and suppression of the host immune response by nematode parasites have been reported extensively and the cysteine protease inhibitor (cystatin) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant cystatin protein from nematode parasite Haemonchus contortus (rHCcyst-2) and investigated its immunomodulatory effects on goat monocyte. rHCcyst-2 protein is biologically functional as shown by its ability to inhibit the protease activity of cathepsin L, cathepsin B and papain. Immunohistochemical test demonstrated that the native HCcyst-2 protein was predominantly localized at the body surface and internal surface of the worm's gut. We demonstrated that rHCcyst-2 could be distinguished by antisera from goats experimentally infected with H. contortus and could uptake by goat monocytes. The immunomodulatory effects of HCcyst-2 on cytokine secretion, MHC molecule expression, NO production and phagocytosis were observed by co-incubation of rHCcyst-2 with goat monocytes. The results showed that the interaction of rHCcyst-2 decreased the production of TNF-α, IL-1β and IL-12p40. However, it significantly increased the secretion of IL-10 in goat monocytes. After rHCcyst-2 exposure, the expression of MHC-II on goat monocytes was inhibited. Moreover, rHCcyst-2 could up-regulate the LPS induced NO production of goat monocytes. Phagocytotic assay by FITC-dextran internalization showed that rHCcyst-2 inhibited the phagocytosis of goat monocytes. Our findings provided potential target as immunoregulator, and will be helpful to illustrate the molecular basis of host-parasite interactions and search for new potential molecule as vaccine and drug target candidate.
- Subjects :
- Amino Acid Sequence
Animals
Cloning, Molecular
Cystatins chemistry
Cystatins genetics
Cystatins isolation & purification
Cytokines biosynthesis
Gene Expression
Goats
Haemonchus
Histocompatibility Antigens Class II genetics
Histocompatibility Antigens Class II immunology
Nitric Oxide biosynthesis
Phagocytosis drug effects
Phagocytosis immunology
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins isolation & purification
Recombinant Proteins pharmacology
Sequence Analysis, DNA
Cystatins pharmacology
Immunomodulation drug effects
Monocytes drug effects
Monocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 8
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 28484087
- Full Text :
- https://doi.org/10.18632/oncotarget.17308