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We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate,  Biomphalaria glabrata , the snail intermediate host of the human blood fluke  Schistosoma mansoni . In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from  B. glabrata  (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the  B. glabrata  embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the  in vitro  encapsulation of  S. mansoni  sporocysts. Furthermore, the  in vivo  knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by  S. mansoni  miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions.

Involvement of the Cytokine MIF in the Snail Host Immune Response to the Parasite Schistosoma mansoni