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.
Highlights
Haemonchus contortus (H. contortus) is one of the most economically important parasites of small ruminants worldwide
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
Summary
Haemonchus contortus (H. contortus) is one of the most economically important parasites of small ruminants worldwide. Molecules expressed and secreted by the nematode that might modulate host immune responses include proteases, protease inhibitors, antioxidants and orthologs of host cytokines and their receptors [7]. Mammalian migration inhibitory factor (MIF) was among the first immune system cytokines to be discovered as a soluble factor released from activated lymphocytes that inhibited random migration of macrophages [8, 9]. The function of macrophage MIF has endured, MIF is recognized as being highly pleiotropic in www.impactjournals.com/oncotarget regulation of innate and adaptive immune cell populations, as well as cells of the neuroendocrine system [10, 11]. MIF have been reported in free living nematode Caenorhabditis elegans and parasitic nematodes such as Trichuris sp., Onchocerca volvulus, Brugia pahangi, Strongolyidis stercoralis, Ancyclostoma sp. and Schistosoma sp. [24]
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