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Selective human cysteine protease inhibition mediates Ixodes scapularis blood feeding success
Author(s) -
Kotsyfakis Michail,
Karim Shahid,
Anderson Jennifer,
Andersen John,
Valenzuela Jesus,
Mather Thomas,
Ribeiro Jose
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.793.3
Subject(s) - ixodes scapularis , biology , tick , ixodes , proteases , vaccination , lyme disease , virology , borrelia burgdorferi , saliva , blood meal , microbiology and biotechnology , immunology , ixodidae , zoology , antibody , biochemistry , enzyme
Ixodes scapularis is the main vector of Lyme disease in the eastern United States. These hematophagous arthropods have developed unique strategies to circumvent vertebrate defense mechanisms and among them, saliva secretion in the sites of infestation has been shown as important for both blood meal completion and pathogen transmission. Here we report a duplication event of cystatin genes in tick genome ‐ named as sialostatins L and L2 ‐ that results in a transcription regulated boost of saliva inhibitory activity against a relatively limited number of vertebrate papain like cysteine proteases during blood meal. Tick treatment with sialostatin L2 dsRNA resulted immediate rejection and subsequent death of 40% of the silenced ticks, when attached on a rabbit. The rest 60% of the silenced ticks that managed to attach to the rabbit they weighed 3 times lesser than the control group after completion of their meal. Given the role of the targeted enzymes in vertebrate immunity, we uncover that host immunomodulation is implicated in the deleterious phenotype of silenced ticks making I. scapularis cystatins attractive targets for the development of anti tick vaccines. Indeed vaccination of guinea pigs with sialostatin L2 protein leads to their protection against tick blood feeding, while on‐going experiments aim to show whether such a vaccination affects Lyme disease transmission as well.