Abstract
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.
Highlights
Schistosomiasis, the second most widespread human parasitic disease after malaria [1], is caused by helminth parasites of the genus Schistosoma and more than 200 million people in 74 countries suffer from the pathological consequences of this disease [2]
We have identified and characterized the involvement of a snail homologue of the cytokine MIF (Macrophage Migration Inhibitory Factor) in the snail immune responses to infection by the parasite
We demonstrate that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features
Summary
Schistosomiasis, the second most widespread human parasitic disease after malaria [1], is caused by helminth parasites of the genus Schistosoma and more than 200 million people in 74 countries suffer from the pathological consequences of this disease [2]. Major signalling pathways or effector molecules underlying innate immune responses of vertebrates and invertebrates are shared, as for instance the Toll receptors described for the first time in Drosophila [4] or members of immunoglobulin superfamily such as the FREPs (Fibrinogen-RElated Proteins) in B. glabrata [5]. MIF was one of the first mammalian cytokines to be discovered and has been described as a pivotal regulator of innate immune and inflammatory responses in mammals [10]. It was first characterized as a factor derived from activated T cells that inhibited random migration of macrophages [11], [12].
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