Sequence, structural homology and phylogenetic relationship among Macrophage migration inhibitory factors (MIF) from Ixodid ticks

The Ixodid tick’s prolonged blood feeding strategies may enhance pathogen transmission. Macrophage Migration Inhibitory Factor (MIF, a pro-inflammatory cytokine) has been identified in four Ixodid tick species. Our hypothesis is that MIF functions in tick blood meal acquisition and pathogen transmission. This bioinformatics-based study compared tick MIF with MIFs from other arthropods and selected parasitic nematode. Homology modeling to identify and develop a potential model for tick MIF structure was also done. Multiple sequence alignment showed a high level of sequence conservation in MIFs among different tick species. A highly conserved, tick-specific amino acid sequence was observed in the alignment. The percentage identity of this region ranged from 73- 91% among ticks and it was from 27- 50% in other arthropods and nematodes. The phylogenetic tree analysis predicted tick MIF sequences were more related to the nematode MIF sequences than to the other arthropod MIFs. The model protein identified for tick MIF was Xenopus laevis (PDB ID: 1uiz) MIF with a 42.609% sequence identity. A high level of sequence conservation and phylogenetic proximity of MIF in ticks and parasitic nematodes suggests selective pressure on parasitism during their evolution. While nematodes may use MIF for delaying immune recognition by lymphocytes during infection, ticks may require MIF to modify the cellular infiltrate in the feeding lesion in order to achieve an adequate blood meal.