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The host inflammatory response contributes to the tissue damage that occurs during amebic colitis, with tumor necrosis factor alpha (TNF-α) being a key mediator of the gut inflammation observed. Mammalian macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the exacerbation of a wide range of inflammatory diseases, including colitis. We identified a MIF gene homolog in theEntamoeba histolytica genome, raising the question of whetherE. histolytica MIF (Eh MIF) has proinflammatory activity similar to that of mammalian MIF. In this report, we describe the first functional characterization ofEh MIF. Antibodies were prepared against recombinantly expressedEh MIF and used to demonstrate thatEh MIF is expressed as a 12-kDa protein localized to the cytoplasm of trophozoites. In a manner similar to that of mammalian MIF,Eh MIF interacted with the MIF receptor CD74 and bound to macrophages.Eh MIF induced interleukin-6 (IL-6) production. In addition,Eh MIF enhanced TNF-α secretion by amplifying TNF-α production by lipopolysaccharide (LPS)-stimulated macrophages and by inhibiting the glucocorticoid-mediated suppression of TNF-α secretion.Eh MIF was expressed during human infection, as evidenced by the presence of anti-Eh MIF antibodies in the sera of children living in an area whereE. histolytica infection is endemic. Anti-Eh MIF antibodies did not cross-react with human MIF. The ability ofEh MIF to modulate host macrophage function may promote an exaggerated proinflammatory immune response and contribute to the tissue damage seen in amebic colitis.

The Macrophage Migration Inhibitory Factor Homolog of Entamoeba histolytica Binds to and Immunomodulates Host Macrophages