Blood in the gut is maintained in a fluid state throughout the process of repletion, and up to 24�C48 h beyond repletion. The anticoagulation mechanisms in the gut have not been addressed at the molecular level. Ticks alternately deposit saliva and suck blood at the tick bite site. It is therefore presumed that tick salivary anticoagulants deposited into the tick bite site are taken up along with the blood, and function both at the vector-host interface and in the tick gut to keep the blood fluid. We now present data to show that the tick gut is not a passive bystander, and that it plays an active role in thwarting host coagulation. We show that the tick gut expresses a thrombin inhibitor, Ixophilin, during tick feeding. These findings open up a new avenue of research, hitherto ignored, that can increase our understanding of tick feeding strategies, and provide novel targets for interrupting tick feeding and pathogen transmission. Tick anticoagulation strategies are central to successful feeding and it is now well documented that the tick utilizes a multipronged strategy to thwart host hemostasis. However, the functional redundancy of the salivary anticoagulome poses a major bottleneck in efforts to develop vaccines targeting specific salivary anticoagulants. We now shift the focus from the tick saliva to the tick gut and draw attention to the role of the tick gut in anticoagulation and reveal a new critical aspect in tick feeding. Ixodid ticks feed for days and imbibe as much as times their body weight of blood meal during engorgement. The tick gut serves as a storage organ for fluid blood conducive for both receptor-mediated and fluid-phase endocytosis of the blood meal by the gut digestive cells. The blood in the gut is maintained in a fluid state throughout the process of repletion and up to 24�C48 hours beyond repletion. Ticks alternately deposit saliva into and suck blood from the tick bite site, and it was presumed that salivary immune modulators and anticoagulants deposited into the bite site, and absorbed into the gut along with the bloodmeal might provide essential functions both at the bite site and in the gut. However, a recent analysis of the gut transcriptome of Dermacentor variabilis by Anderson et al showed that about 6 of the sequenced Iloprost transcripts encoded secreted proteins with putative antioxidant, anticoagulant and antimicrobial functions distinct from that observed in salivary glands. Consistent with this emerging active role for the tick gut in feeding, several DMXAA reports demonstrate the expression of gut-specific anticoagulants in several Ixodid ticks.
