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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Autores principales: 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
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Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/04d733e57990492a87e41a1f3a61d082
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle 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
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