Pathogen Entrapment by Transglutaminase—A Conserved Early Innate Immune Mechanism

PLoS Pathogens

Torsten G. Loof¹  Olga Loseva¹  Ulrich Theopold²  Heiko Herwald²  Pavel Dobes³  Richard M. Cripps³  Jennifer Iklé⁴  Zhi Wang⁵  Christine Wilhelmsson⁵  Matthias Mörgelin⁵  Pavel Hyrsl⁵  Martina Klupp⁵ 

[1] Department of Animal Physiology and Immunology, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic;Department of Biology, University of New Mexico, Albuquerque, New Mexico, United States of America;Department of Clinical Sciences, Lund University, Lund, Sweden;Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden;Department of Molecular Biology and Functional Genomics, Stockholm University, Stockholm, Sweden

关键词: Larvae;    Nematode infections;    Bacteria;    Drosophila melanogaster;    Staphylococcus aureus;    Insects;    Blood;    Immunity;   

DOI  :  10.1371/journal.ppat.1000763

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY