Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism.
Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism.
复制标题
DOI：
10.1371/journal.ppat.1000763
复制
发表时间：
2010-02-12
期刊：
影响因子：
6.7
通讯作者：
Theopold U
中科院分区：
文献类型：
--
作者：
Wang Z;Wilhelmsson C;Hyrsl P;Loof TG;Dobes P;Klupp M;Loseva O;Mörgelin M;Iklé J;Cripps RM;Herwald H;Theopold U
Clotting systems are required in almost all animals to prevent loss of body fluids after injury. Here, we show that despite the risks associated with its systemic activation, clotting is a hitherto little appreciated branch of the immune system. We compared clotting of human blood and insect hemolymph to study the best-conserved component of clotting systems, namely the Drosophila enzyme transglutaminase and its vertebrate homologue Factor XIIIa. Using labelled artificial substrates we observe that transglutaminase activity from both Drosophila hemolymph and human blood accumulates on microbial surfaces, leading to their sequestration into the clot. Using both a human and a natural insect pathogen we provide functional proof for an immune function for transglutaminase (TG). Drosophila larvae with reduced TG levels show increased mortality after septic injury. The same larvae are also more susceptible to a natural infection involving entomopathogenic nematodes and their symbiotic bacteria while neither phagocytosis, phenoloxidase or—as previously shown—the Toll or imd pathway contribute to immunity. These results firmly establish the hemolymph/blood clot as an important effector of early innate immunity, which helps to prevent septic infections. These findings will help to guide further strategies to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions. One of the main functions of immune systems is to prevent the dissemination of microbes and the resulting sepsis. Blood clotting during sepsis has until now been primarily regarded as harmful, leading to the formation of widespread clots in blood vessels and as a result to organ failure. Here we show that clotting also has a protective function to limit and prevent infections. This is achieved by capturing bacteria in the clot. Our infection studies were performed in the insect model Drosophila melanogaster where, due to the presence of an open circulatory system, the negative effects of clotting are less pronounced. We show that clotting of hemolymph—the insect blood equivalent—is essential in Drosophila to prevent septic death arising from injection of bacteria or infection with a natural pathogen. We also show that both Drosophila transglutaminase and its human homologue clotting factor XIII are key enzymes for sequestration of bacteria in the clot matrix, indicating the conserved nature of the clot's function in immunity. Our data are expected to lead to a much stronger appreciation of the role of blood clotting in innate immunity, and will guide future therapies which target this process.
登录
查看更多内容
影响因子：
2.7
作者：
Rämet, M;Lanot, R;Manfruelli, P
通讯作者：
Manfruelli, P
影响因子：
2.9
作者：
Beresford, PJ;BasinskiGray, JM;Aston, WP
通讯作者：
Aston, WP
影响因子：
5.3
作者：
Bengtson, Sara H.;Sanden, Caroline;Herwald, Heiko
通讯作者：
Herwald, Heiko
DOI：
10.1007/bf01967800
发表时间：
1992-11-01
影响因子：
4.5
作者：
ROTSTEIN, OD
通讯作者：
ROTSTEIN, OD
影响因子：
2.6
作者：
ROWLEY, AF;RATCLIFFE, NA
通讯作者：
RATCLIFFE, NA