Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism.
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 hemolym...
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2010
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oai:doaj.org-article:04d733e57990492a87e41a1f3a61d0822021-11-25T05:48:18ZPathogen entrapment by transglutaminase--a conserved early innate immune mechanism.1553-73661553-737410.1371/journal.ppat.1000763https://doaj.org/article/04d733e57990492a87e41a1f3a61d0822010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20169185/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Clotting 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.Zhi WangChristine WilhelmssonPavel HyrslTorsten G LoofPavel DobesMartina KluppOlga LosevaMatthias MörgelinJennifer IkléRichard M CrippsHeiko HerwaldUlrich TheopoldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 2, p e1000763 (2010) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Zhi Wang Christine Wilhelmsson Pavel Hyrsl Torsten G Loof Pavel Dobes Martina Klupp Olga Loseva Matthias Mörgelin Jennifer Iklé Richard M Cripps Heiko Herwald Ulrich Theopold Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
description |
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. |
format |
article |
author |
Zhi Wang Christine Wilhelmsson Pavel Hyrsl Torsten G Loof Pavel Dobes Martina Klupp Olga Loseva Matthias Mörgelin Jennifer Iklé Richard M Cripps Heiko Herwald Ulrich Theopold |
author_facet |
Zhi Wang Christine Wilhelmsson Pavel Hyrsl Torsten G Loof Pavel Dobes Martina Klupp Olga Loseva Matthias Mörgelin Jennifer Iklé Richard M Cripps Heiko Herwald Ulrich Theopold |
author_sort |
Zhi Wang |
title |
Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
title_short |
Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
title_full |
Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
title_fullStr |
Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
title_full_unstemmed |
Pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
title_sort |
pathogen entrapment by transglutaminase--a conserved early innate immune mechanism. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doaj.org/article/04d733e57990492a87e41a1f3a61d082 |
work_keys_str_mv |
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