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

被引:53
作者
Horka, Helena [2 ,3 ]
Staudt, Valerie [1 ]
Klein, Matthias [1 ]
Taube, Christian [4 ]
Reuter, Sebastian [5 ]
Dehzad, Nina [5 ]
Andersen, John F. [6 ]
Kopecky, Jan [2 ,3 ]
Schild, Hansjoerg [1 ]
Kotsyfakis, Michalis [2 ,3 ]
Hoffmann, Markus [1 ]
Gerlitzki, Bastian [1 ]
Stassen, Michael [1 ]
Bopp, Tobias [1 ]
Schmitt, Edgar [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, D-55131 Mainz, Germany
[2] Univ S Bohemia, Inst Parasitol, Ctr Biol, Acad Sci Czech Republ, Ceske Budejovice 37005, Czech Republic
[3] Univ S Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic
[4] Leiden Univ, Dept Pulmonol, Med Ctr, NL-2333 ZA Leiden, Netherlands
[5] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Med Clin 3, D-55131 Mainz, Germany
[6] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA
关键词
CELL-MEDIATED SUPPRESSION; CD4(+) T-CELLS; IXODES-SCAPULARIS; AIRWAY INFLAMMATION; EPITHELIAL-CELLS; TGF-BETA; INTERLEUKIN; 9; EXPRESSION; ANTIBODY; DISEASE;
D O I
10.4049/jimmunol.1100529
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. The Journal of Immunology, 2012, 188: 2669-2676.
引用
收藏
页码:2669 / 2676
页数:8
相关论文
共 42 条
[21]   Interleukin 9 promotes influx and local maturation of eosinophils [J].
Louahed, J ;
Zhou, YH ;
Maloy, WL ;
Rani, PU ;
Weiss, C ;
Tomer, Y ;
Vink, A ;
Renauld, JC ;
Van Snick, J ;
Nicolaides, NC ;
Levitt, RC ;
Haczku, A .
BLOOD, 2001, 97 (04) :1035-1042
[22]   INDUCTION BY ANTIGEN OF INTRATHYMIC APOPTOSIS OF CD4+CD8+TCRLO THYMOCYTES INVIVO [J].
MURPHY, KM ;
HEIMBERGER, AB ;
LOH, DY .
SCIENCE, 1990, 250 (4988) :1720-1723
[23]   Interleukin 9: A candidate gene for asthma [J].
Nicolaides, NC ;
Holroyd, KJ ;
Ewart, SL ;
Eleff, SM ;
Kiser, MB ;
Dragwa, CR ;
Sullivan, CD ;
Grasso, L ;
Zhang, LY ;
Messler, CJ ;
Zhou, TY ;
Kleeberger, SR ;
Buetow, KH ;
Levitt, RC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (24) :13175-13180
[24]   The Lyme disease agent exploits a tick protein to infect the mammalian host [J].
Ramamoorthi, N ;
Narasimhan, S ;
Pal, U ;
Bao, FK ;
Yang, XFF ;
Fish, D ;
Anguita, J ;
Norgard, MV ;
Kantor, FS ;
Anderson, JF ;
Koski, RA ;
Fikrig, E .
NATURE, 2005, 436 (7050) :573-577
[25]   Mast cell-derived tumour necrosis factor is essential for allergic airway disease [J].
Reuter, S. ;
Heinz, A. ;
Sieren, M. ;
Wiewrodt, R. ;
Gelfand, E. W. ;
Stassen, M. ;
Buhl, R. ;
Taube, C. .
EUROPEAN RESPIRATORY JOURNAL, 2008, 31 (04) :773-782
[26]   Prostaglandin E2 is a major inhibitor of dendritic cell maturation and function in Ixodes scapularis saliva [J].
Sa-Nunes, Anderson ;
Bafica, Andre ;
Lucas, David A. ;
Conrads, Thomas P. ;
Veenstra, Timothy D. ;
Andersen, John F. ;
Mather, Thomas N. ;
Ribeiro, Jose M. C. ;
Francischetti, Ivo M. B. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (03) :1497-1505
[27]   The Immunomodulatory Action of Sialostatin L on Dendritic Cells Reveals Its Potential to Interfere with Autoimmunity [J].
Sa-Nunes, Anderson ;
Bafica, Andre ;
Antonelli, Lis R. ;
Choi, Eun Young ;
Francischetti, Ivo M. B. ;
Andersen, John F. ;
Shi, Guo-Ping ;
Chavakis, Triantafyllos ;
Ribeiro, Jose M. ;
Kotsyfakis, Michalis .
JOURNAL OF IMMUNOLOGY, 2009, 182 (12) :7422-7429
[28]  
SCHMITT E, 1994, J IMMUNOL, V153, P3989
[29]  
SCHMITT E, 1991, J IMMUNOL, V147, P3848
[30]   Helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-Producing macrophages [J].
Schnoeller, Corinna ;
Rausch, Sebastian ;
Pillai, Smitha ;
Avagyan, Angela ;
Wittig, Bianca M. ;
Loddenkemper, Christoph ;
Hamann, Alf ;
Hamelmann, Eckard ;
Lucius, Richard ;
Hartmann, Susanne .
JOURNAL OF IMMUNOLOGY, 2008, 180 (06) :4265-4272