Characterization of a secreted macrophage migration inhibitory factor homologue of the parasitic nematode Haemonchus Contortus acting at the parasite-host cell interface

Abstract

Modulation and suppression of the immune response of the host by nematode parasites have been reported extensively and the migration inhibitory factor (MIF) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant MIF protein from the small ruminant’s nematode parasite Haemonchus contortus (rHCMIF-1), and investigated its immunomodulatory effects on goat monocyte. Enzymatic assays indicated that rHCMIF-1 possessed tautomerase activity. Immunohistochemical test demonstrated that the native HCMIF-1 protein was predominantly localized at the body surface and internal surface of the worm’s gut. We demonstrated that rHCMIF-1 could be distinguished by antisera from goats experimentally infected with H. contortus and could bind by goat monocytes. The immunomodulatory effects of HCMIF-1 on cytokine secretion, MHC molecule expression, NO production and phagocytosis were observed by co-incubation of rHCMIF-1 with goat monocytes. The results showed that the interaction of rHCMIF-1 decreased the production of TNF-α, IL-1β and IL-12p40, where as, it significantly increased the secretion of IL-10 and TGF β in goat monocytes. After rHCMIF-1 exposure, the expression of MHC-II on goat monocytes was inhibited. Moreover, rHCMIF-1 could down-regulate the LPS induced NO production of goat monocytes. Phagocytotic assay by FITC-dextran internalization showed that rHCMIF-1 could inhibit the phagocytosis of goat monocytes. Our findings provided potential targetas immunoregulator, and will be helpful to elucidate the molecular basis of host–parasite interactions and search for new potential protein as vaccine and drug target candidate.