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

Strongyloidiasis is a tropical parasitosis characterized by an alternation between free-living and parasitic stages, and by long-term infection via autoinfection. Since invasion and evasion processes of helminth parasites are substantially attained by the involvement of excretory-secretory products, we identified and characterized the 13.5 kDa macrophage migration inhibitory factor (MIF)-like protein in Strongyloides ratti. Sra-MIF is mainly secreted from the infective stage larvae (iL3), while the transcript was found at lower levels in parasitic and free-living females. Sequence analysis of the full-length cDNA showed the highest homology to the human pathogen Strongyloides stercoralis, and both are related to the MIF type-2. Unlike other mif genes, the Sra-mif includes no intron. The protein was recombinantly expressed in Escherichia coli and purified. Sra-MIF exhibited no in vitro tautomerase activity. The exposure of Sra-MIF to the host immune system is confirmed by high IgG reactivities found in the hosts' sera following infection or immunization. Flow cytometric analysis indicated the binding of Sra-MIF to the monocytes/macrophage lineage but not to peripheral lymphocytes. After exposure to Sra-MIF, monocytes released IL-10 but not TNF-alpha suggesting the involvement of the secreted parasite MIF in host immune responses.