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      Heterorhabditis bacteriophora Excreted-Secreted Products Enable Infection by Photorhabdus luminescens Through Suppression of the Imd Pathway

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          Abstract

          Upon entering the hemocoel of its insect host, the entomopathogenic nematode Heterorhabditis bacteriophora releases its symbiotic bacteria Photorhabdus luminescens, which is also a strong insect pathogen. P. luminescens is known to suppress the insect immune response independently following its release, but the nematode appears to enact its own immunosuppressive mechanisms during the earliest phases of an infection. H. bacteriophora was found to produce a unique set of excreted-secreted proteins in response to host hemolymph, and while basal secretions are immunogenic with regard to Diptericin expression through the Imd pathway, host-induced secretions suppress this expression to a level below that of controls in Drosophila melanogaster. This effect is consistent in adults, larvae, and isolated larval fat bodies, and the magnitude of suppression is dose-dependent. By reducing the expression of Diptericin, an antimicrobial peptide active against Gram-negative bacteria, the activated excreted-secreted products enable a more rapid propagation of P. luminescens that corresponds to more rapid host mortality. The identification and isolation of the specific proteins responsible for this suppression represents an exciting field of study with potential for enhancing the biocontrol of insect pests and treatment of diseases associated with excessive inflammation.

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          Most cited references43

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          The Drosophila imd signaling pathway.

          The fruit fly, Drosophila melanogaster, has helped us to understand how innate immunity is activated. In addition to the Toll receptor and the Toll signaling pathway, the Drosophila immune response is regulated by another evolutionarily conserved signaling cascade, the immune deficiency (Imd) pathway, which activates NF-κB. In fact, the Imd pathway controls the expression of most of the antimicrobial peptides in Drosophila; thus, it is indispensable for normal immunity in flies. In this article, we review the current literature on the Drosophila Imd pathway, with special emphasis on its role in the (patho)physiology of different organs. We discuss the systemic response, as well as local responses, in the epithelial and mucosal surfaces and the nervous system.
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            A METHOD FOR OBTAINING INFECTIVE NEMATODE LARVAE FROM CULTURES.

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              Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia.

              The production of antimicrobial peptides is an important aspect of host defense in multicellular organisms. In Drosophila, seven antimicrobial peptides with different spectra of activities are synthesized by the fat body during the immune response and secreted into the hemolymph. Using GFP reporter transgenes, we show here that all seven Drosophila antimicrobial peptides can be induced in surface epithelia in a tissue-specific manner. The imd gene plays a critical role in the activation of this local response to infection. In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                04 October 2019
                2019
                : 10
                : 2372
                Affiliations
                [1] 1Infection and Innate Immunity Lab, Department of Biological Sciences, George Washington University , Washington, DC, United States
                [2] 2Department of Microbiology, Immunology, and Tropical Medicine, George Washington University , Washington, DC, United States
                [3] 3Institute for Neuroscience, Department of Biological Sciences, George Washington University , Washington, DC, United States
                Author notes

                Edited by: Susanna Valanne, University of Tampere, Finland

                Reviewed by: Anchalee -Tassanakajon, Chulalongkorn University, Thailand; Friederike Ebner, Free University of Berlin, Germany

                *Correspondence: Ioannis Eleftherianos ioannise@ 123456gwu.edu

                This article was submitted to Comparative Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2019.02372
                6787769
                30723466
                38f39089-d9e0-465a-b647-fbdb048c08aa
                Copyright © 2019 Kenney, Hawdon, O'Halloran and Eleftherianos.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 July 2019
                : 20 September 2019
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 45, Pages: 14, Words: 9888
                Categories
                Immunology
                Original Research

                Immunology
                parasitic nematode,drosophila,innate immunity,imd pathway,heterorhabditis,photorhabdus
                Immunology
                parasitic nematode, drosophila, innate immunity, imd pathway, heterorhabditis, photorhabdus

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