| Host-derived extracellular nucleic acids enhance innate immune responses, induce coagulation, and prolong survival upon infection in insects. | |
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MedLine Citation:
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PMID: 18684961 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Extracellular nucleic acids play important roles in human immunity and hemostasis by inducing IFN production, entrapping pathogens in neutrophil extracellular traps, and providing procoagulant cofactor templates for induced contact activation during mammalian blood clotting. In this study, we investigated the functions of extracellular RNA and DNA in innate immunity and hemolymph coagulation in insects using the greater wax moth Galleria mellonella a reliable model host for many insect and human pathogens. We determined that coinjection of purified Galleria-derived nucleic acids with heat-killed bacteria synergistically increases systemic expression of antimicrobial peptides and leads to the depletion of immune-competent hemocytes indicating cellular immune stimulation. These activities were abolished when nucleic acids had been degraded by nucleic acid hydrolyzing enzymes prior to injection. Furthermore, we found that nucleic acids induce insect hemolymph coagulation in a similar way as LPS. Proteomic analyses revealed specific RNA-binding proteins in the hemolymph, including apolipoproteins, as potential mediators of the immune response and hemolymph clotting. Microscopic ex vivo analyses of Galleria hemolymph clotting reactions revealed that oenocytoids (5-10% of total hemocytes) represent a source of endogenously derived extracellular nucleic acids. Finally, using the entomopathogenic bacterium Photorhabdus luminescens as an infective agent and Galleria caterpillars as hosts, we demonstrated that injection of purified nucleic acids along with P. luminescens significantly prolongs survival of infected larvae. Our results lend some credit to our hypothesis that host-derived nucleic acids have independently been co-opted in innate immunity of both mammals and insects, but exert comparable roles in entrapping pathogens and enhancing innate immune responses. |
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Authors:
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Boran Altincicek; Sabine Stötzel; Malgorzata Wygrecka; Klaus T Preissner; Andreas Vilcinskas |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 181 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-08-07 Completed Date: 2008-10-06 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2705-12 Citation Subset: AIM; IM |
Affiliation:
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Institute of Phytopathology and Applied Zoology, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, Giessen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apolipoproteins / physiology DNA / administration & dosage* Extracellular Fluid / immunology, microbiology Gram-Negative Bacterial Infections / immunology, microbiology, prevention & control Hemolymph / immunology*, microbiology Hemostasis / immunology Humans Immunity, Cellular* / genetics Immunity, Innate* / genetics Larva / genetics, growth & development, immunology, microbiology Moths / growth & development*, immunology*, microbiology Photorhabdus / genetics, immunology*, pathogenicity Proteome / immunology RNA / administration & dosage* RNA-Binding Proteins / physiology |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins; 0/Proteome; 0/RNA-Binding Proteins; 63231-63-0/RNA; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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