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.
Highlights
The cystatins belongs to superfamily of enzymes which consists of evolutionary tight-binding inhibitors to form reversible complexes of papain-like cysteine proteases [1]
We demonstrated that rHCcyst-2 could be distinguished by antisera from goats experimentally infected with H. contortus and could uptake by goat monocytes
We found that the recombinant cystatin from H. contortus significantly modulated goat monocyte function in multiple aspects
Summary
The cystatins belongs to superfamily of enzymes which consists of evolutionary tight-binding inhibitors to form reversible complexes of papain-like cysteine proteases [1]. The gastrointestinal nematodes or parasites which exist within tissues of their hosts continuously exposed to a www.impactjournals.com/oncotarget range of immune effector mechanisms. To survive within the host environment, parasites has to adopt a strategy to manage within the immune responses by the release of immunomodulatory constituents that halt effector mechanisms or intermingle with the cytokine network [11]. Both complexity of mammalian innate and adaptive immune mechanisms and the long co-evolutionary association during host-parasite interface, play a considerable role in the number of molecular interactions [12]. Many studies have been conducted in recent years, which shown that cystatins from various nematode parasites act as major immune modulators during host parasite interactions [4, 13]
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