Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis.
Here we report the ability of the tick Ixodes scapularis, the main vector of Lyme disease in the United States, to actively and specifically affect the host proteolytic activity in the sites of infestation through the release of a cystatin constituent of its saliva. The cystatin presence in the saliva was verified both biochemically and immunologically. We named the protein sialostatin L because of its inhibitory action against cathepsin L. We also show that the proteases it targets, although limited in number, have a prominent role in the proteolytic cascades that take place in the extracellular and intracellular environment. As a result, sialostatin L displays an antiinflammatory role and inhibits proliferation of cytotoxic T lymphocytes. Beyond unraveling another component accounting for the properties of tick saliva, contributing to feeding success and pathogen transmission, we describe a novel tool for studying the role of papain-like proteases in diverse biologic phenomena and a protein with numerous potential pharmaceutical applications.
Kotsyfakis
Michalis
M
Vector Biology Section, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20852, USA.
Sá-Nunes
Anderson
A
Francischetti
Ivo M B
IM
Mather
Thomas N
TN
Andersen
John F
JF
Ribeiro
José M C
JM
D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002460:Cell Line; D019295:Computational Biology; D015891:Cystatins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D019476:Insect Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018884:Ixodes / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D012463:Saliva / Q000737:chemistry*; D016415:Sequence Alignment
D000893:Anti-Inflammatory Agents; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D007166:Immunosuppressive Agents; D019476:Insect Proteins; C515505:sialostatin L, Ixodes scapularis; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse