The tick salivary protein sialostatin L inhibits the Th9-derived production of the asthma-promoting cytokine IL-9 and is effective in the prevention of experimental asthma.
Ticks developed a multitude of different immune evasion strategies to obtain a blood meal. Sialostatin L is an immunosuppressive cysteine protease inhibitor present in the saliva of the hard tick Ixodes scapularis. In this study, we demonstrate that sialostatin L strongly inhibits the production of IL-9 by Th9 cells. Because we could show recently that Th9-derived IL-9 is essentially involved in the induction of asthma symptoms, sialostatin L was used for the treatment of experimental asthma. Application of sialostatin L in a model of experimental asthma almost completely abrogated airway hyperresponsiveness and eosinophilia. Our data suggest that sialostatin L can prevent experimental asthma, most likely by inhibiting the IL-9 production of Th9 cells. Thus, alternative to IL-9 neutralization sialostatin L provides the basis for the development of innovative therapeutic strategies to treat asthma.
Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic and Faculty of Science, University of South Bohemia, 37005 České Budějovice, Czech Republic.
Helena
H
Horka
Valérie
V
Staudt
Matthias
M
Klein
Christian
C
Taube
Sebastian
S
Reuter
Nina
N
Dehzad
John F
JF
Andersen
Jan
J
Kopecky
Hansjörg
H
Schild
Michalis
M
Kotsyfakis
Markus
M
Hoffmann
Bastian
B
Gerlitzki
Michael
M
Stassen
Tobias
T
Bopp
Edgar
E
Schmitt
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D002469:Cell Separation; D015891:Cystatins / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016906:Interleukin-9 / Q000096:biosynthesis / Q000276:immunology*; D026863:Ixodidae / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D015891:Cystatins; D016207:Cytokines; D016906:Interleukin-9; C515505:sialostatin L, Ixodes scapularis