Drosophila innate immunity and response to fungal infections

Department of Biology, Stanford University, Stanford, CA 94305-5020, USA.
Cellular Microbiology (Impact Factor: 4.92). 06/2008; 10(5):1021-6. DOI: 10.1111/j.1462-5822.2008.01120.x
Source: PubMed


The fruit fly Drosophila melanogaster is an important model for the analysis of the interaction between host immune systems and fungal pathogens. Recent experiments have extended our understanding of the Toll-based signalling pathway critical to response to fungal infections, and identified new elements involved in cellular and humoral-based defences. The fly immune system shows remarkable sophistication in its ability to discriminate among pathogens, and the powerful genetics available to researchers studying the adult fly response, and the ability to manipulate cultured phagocytic cell lines with RNAi, are allowing researchers to dissect the molecular details of the process.

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Available from: Malcolm Whiteway, Oct 13, 2014
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    • "identity) of yeast PMT4 O-mannosyltransferase involved in protein O-mannosylation/glycosylation and determining the structure and integrity of fungal cell walls (Lengeler et al., 2008). It is well-known that fungal cell wall components (mainly the glucans) are the primary pathogenassociated molecular patterns that trigger insect Toll pathway to induce immune responses (Gottar et al., 2006; Levitin and Whiteway, 2008).Thus, upregulation of these genes, if not all, in ΔMrpacC could lead to mutant cell wall remodelling that in turn would trigger stronger insect immune responses. Thus, it could be concluded that MrpacC contributes to fungal virulence by maintaining cell wall integrity/remodelling in insect haemocoels. "
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    ABSTRACT: pH-responsive transcription factor of the PacC/Rim101 family governs adaptation to environment, development and virulence in many fungal pathogens. In this study, we report the functions of a PacC homolog, MrpacC, in an insect pathogenic fungus Metarhizium robertsii. The gene was highly transcribed in the fungus in alkaline conditions and deletion of MrpacC impaired fungal responses to ambient pH and salt/metal challenges but not osmotic stress. We found that MrpacC is required for fungal full virulence by contributing to penetration of insect cuticles, mycosis of insect cadavers and evasion of host immunity. In MrpacC deletion strains, the chitinase but not protease activity was reduced, which was consistent with the down-regulation of Groups A and C chitinase genes. Further, the glucosyltransferase genes involved in cell wall remodeling and protein glycosylation were up-regulated in ΔMrpacC. MrpacC transcriptional control of chitinase and glucosyltransferase genes was verified both by the presence of PacC consensus binding motif in gene promoter regions and the promoter DNA binding assays. The results of this study not only advances the understanding of PacC function in fungal development and virulence but will also facilitate future studies on the mechanism(s) behind the selective control of target genes by PacC.
    Environmental Microbiology 04/2015; 17(4):994-1008. DOI:10.1111/1462-2920.12451 · 6.20 Impact Factor
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    • "There have been many reports on AMPs from various insect species, but very few reviews on insect AMPs (Imler and Bulet 2005; Li et al. 2006). Several reviews related to insect AMPs are mainly from Drosophila with a focus on activation of AMPs in response to various infections or regulation of AMP gene expressions by the Toll and IMD signaling pathways (Fullaondo and Lee 2012; Hetru and Hoffmann 2009; Lazzaro 2008; Lemaitre and Hoffmann 2007; Levitin and Whiteway 2008; Moy and Cherry 2013). Antiparasitic peptides and antimalarial peptides have been reviewed recently (Bell 2011; Pretzel et al. 2013). "
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    ABSTRACT: Insects are one of the major sources of antimicrobial peptides/proteins (AMPs). Since observation of antimicrobial activity in the hemolymph of pupae from the giant silk moths Samia Cynthia and Hyalophora cecropia in 1974 and purification of first insect AMP (cecropin) from H. cecropia pupae in 1980, over 150 insect AMPs have been purified or identified. Most insect AMPs are small and cationic, and they show activities against bacteria and/or fungi, as well as some parasites and viruses. Insect AMPs can be classified into four families based on their structures or unique sequences: the α-helical peptides (cecropin and moricin), cysteine-rich peptides (insect defensin and drosomycin), proline-rich peptides (apidaecin, drosocin, and lebocin), and glycine-rich peptides/proteins (attacin and gloverin). Among insect AMPs, defensins, cecropins, proline-rich peptides, and attacins are common, while gloverins and moricins have been identified only in Lepidoptera. Most active AMPs are small peptides of 20-50 residues, which are generated from larger inactive precursor proteins or pro-proteins, but gloverins (~14 kDa) and attacins (~20 kDa) are large antimicrobial proteins. In this mini-review, we will discuss current knowledge and recent progress in several classes of insect AMPs, including insect defensins, cecropins, attacins, lebocins and other proline-rich peptides, gloverins, and moricins, with a focus on structural-functional relationships and their potential applications.
    Applied Microbiology and Biotechnology 05/2014; 98(13). DOI:10.1007/s00253-014-5792-6 · 3.34 Impact Factor
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    • ", 2004 ; Michel et al . , 2001 ; Levitin and Whiteway , 2008 ) . Once activated , these pathways trigger an intracellular cascade , culminating in the rapid and robust production of antimicrobial peptides . "
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    ABSTRACT: Innate immunity is the first line of defense against invading pathogens. Vertebrate innate immunity provides both initial protection, and activates adaptive immune responses, including memory. As a result, the study of innate immune signaling is crucial for understanding the interactions between host and pathogen. Unlike mammals, the insect Drosophila melanogaster lack classical adaptive immunity, relying on innate immune signaling via the Toll and IMD pathways to detect and respond to invading pathogens. Once activated these pathways lead to the rapid and robust production of a variety of antimicrobial peptides. These peptides are secreted directly into the hemolymph and assist in clearance of the infection. The genetic and molecular tools available in the Drosophila system make it an excellent model system for studying immunity. Furthermore, the innate immune signaling pathways used by Drosophila show strong homology to those of vertebrates making them ideal for the study of activation, regulation and mechanism. Currently a number of questions remain regarding the activation and regulation of both vertebrate and insect innate immune signaling. Over the past years many proteins have been implicated in mammalian and insect innate immune signaling pathways, however the mechanisms by which these proteins function remain largely undetermined. My work has focused on understanding the molecular mechanisms of innate immune activation in Drosophila. In these studies I have identified a number of novel protein/protein interactions which are vital for the activation and regulation of innate immune induction. This work shows that upon stimulation the Drosophila protein IMD is cleaved by the caspase-8 homologue DREDD. Cleaved IMD then binds the E3 ligase DIAP2 and promotes the K63-polyubiquitination of IMD and activation of downstream signaling. Furthermore the Yersinia pestis effector protein YopJ is able to inhibit the critical IMD pathway MAP3 kinase TAK1 by serine/threonine-acetylation of its activation loop. Lastly TAK1 signaling to the downstream Relish/NF-κB and JNK signaling pathways can be regulated by two isoforms of the TAB2 protein. This work elucidates the molecular mechanism of the IMD signaling pathway and suggests possible mechanisms of homologous mammalian systems, of which the molecular details remain unclear.
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