Abstract

Ticks, lice, flees, mosquitos, leeches and vampire bats need to prevent the host’s blood coagulation during their feeding process. This is primarily achieved by injecting potent anticoagulant proteins. Basophils frequently accumulate at the site of tick feeding. However, this occurs only after the second encounter with the parasite involving an adaptive immune response and IgE. To study the potential role of basophils and mast cells in the defense against ticks and other ectoparasites, we produced anticoagulant proteins from three blood-feeding animals; tick, mosquito, and leech. We tested these anticoagulant proteins for their sensitivity to inactivation by a panel of hematopoietic serine proteases. The majority of the connective tissue mast cell proteases tested, originating from humans, dogs, rats, hamsters, and opossums, efficiently cleaved these anticoagulant proteins. Interestingly, the mucosal mast cell proteases that contain closely similar cleavage specificity, had little effect on these anticoagulant proteins. Ticks have been shown to produce serpins, serine protease inhibitors, upon a blood meal that efficiently inhibit the human mast cell chymase and cathepsin G, indicating that ticks have developed a strategy to inactivate these proteases. We show here that one of these tick serpins (IRS-2) shows broad activity against the majority of the mast cell chymotryptic enzymes and the neutrophil proteases from human to opossum. However, it had no effect on the mast cell tryptases or the basophil specific protease mMCP-8. The production of anticoagulants, proteases and anti-proteases by the parasite and the host presents a fascinating example of an arms race between the blood-feeding animals and the mammalian immune system with an apparent and potent role of the connective tissue mast cell chymases in the host defense.

Highlights

  • Introduction published maps and institutional affilTicks, lice, flees, mosquitos, leeches and vampire bats need blood as a food source and for their reproduction

  • The question we address here is if mast cell and basophil serine proteases are directly involved in the defense against ectoparasites

  • As the first step in the search for a potential role of the different hematopoietic serine proteases in the defense against ectoparasites, we analyzed their activity against Tick Anticoagulant Protein (TAP), a potent anticoagulant protein expressed by the tick Ornithodoros moubata [9]

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Summary

Introduction

Lice, flees, mosquitos, leeches and vampire bats need blood as a food source and for their reproduction. One problem for these ectoparasites is that blood very coagulates when placed in contact with foreign material and several of these blood-feeding animals feed for a relatively long period, sometimes several days or weeks. These bloodfeeding animals, produce potent anticoagulant proteins, potent complement inactivating proteins, anesthetics, immunosuppressives, profibrinolytics, and compounds that promote vasodilation [1,2,3,4,5]. Anophelins act primarily by blocking thrombin exosite 1, but with an opposite orientation of the peptide iations

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