A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A2-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity

Yajima, Masashi; Takada, Masatoshi; Takahashi, Nahoko; Kikuchi, Haruhisa; Natori, Shunji; Oshima, Yoshiteru; Kurata, Shoichiro

doi:10.1042/bj20021603

Cited by 96 publications

(68 citation statements)

References 33 publications

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“…This idea is consistent with the reported link in the dipteran Drosophila melanogaster between eicosanoid biosynthesis and the immune deficiency (IMD) pathway signaling system, one of the signaling pathways responsible for induction of AMP expression (19). However, since X. nematophila inhibits the expression of genes encoding AMPs in lepidopterans (3,4,20) but not D. melanogaster insects (21,22), it appears that X. nematophila targets a step in AMP induction that is present in Lepidoptera but not D. melanogaster.…”

supporting

confidence: 78%

The Global Transcription Factor Lrp Is both Essential for and Inhibitory to Xenorhabdus nematophila Insecticidal Activity

Casanova-Torres

Shokal

Morag

et al. 2017

Appl Environ Microbiol

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In the entomopathogenic bacterium Xenorhabdus nematophila, cell-tocell variation in the abundance of the Lrp transcription factor leads to virulence modulation; low Lrp levels are associated with a virulent phenotype and suppression of antimicrobial peptides (AMPs) in Manduca sexta insects, while cells that lack lrp or express high Lrp levels are virulence attenuated and elicit AMP expression. To better understand the basis of these phenotypes, we examined X. nematophila strains expressing fixed Lrp levels. Unlike the lrp-null mutant, the high-lrp strain is fully virulent in Drosophila melanogaster, suggesting that these two strains have distinct underlying causes of virulence attenuation in M. sexta. Indeed, the lrp-null mutant was defective in cytotoxicity against M. sexta hemocytes relative to that in the high-lrp and low-lrp strains. Further, supernatant derived from the lrp-null mutant but not from the high-lrp strain was defective in inhibiting weight gain when fed to 1st instar M. sexta. These data suggest that contributors to the lrp-null mutant virulence attenuation phenotype are the lack of Lrp-dependent cytotoxic and extracellular oral growth inhibitory activities, which may be particularly important for virulence in D. melanogaster. In contrast, the high-Lrp strain was sensitive to the antimicrobial peptide cecropin, had a transient survival defect in M. sexta, and had reduced extracellular levels of insecticidal activity, measured by injection of supernatant into 4th instar M. sexta. Thus, high-lrp strain virulence attenuation may be explained by its hypersensitivity to M. sexta host immunity and its inability to secrete one or more insecticidal factors.IMPORTANCE Adaptation of a bacterial pathogen to host environments can be achieved through the coordinated regulation of virulence factors that can optimize success under prevailing conditions. In the insect pathogen Xenorhabdus nematophila, the global transcription factor Lrp is necessary for virulence when injected into Manduca sexta or Drosophila melanogaster insect hosts. However, high levels of Lrp, either naturally occurring or artificially induced, cause attenuation of X. nematophila virulence in M. sexta but not D. melanogaster. Here, we present evidence suggesting that the underlying cause of high-Lrp-dependent virulence attenuation in M. sexta is hypersensitivity to host immune responses and decreased insecticidal activity and that high-Lrp virulence phenotypes are insect host specific. This knowledge suggests that X. nematophila faces varied challenges depending on the type of insect host it infects and that its success in these environments depends on Lrp-dependent control of a multifactorial virulence repertoire.

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supporting

confidence: 78%

The Global Transcription Factor Lrp Is both Essential for and Inhibitory to Xenorhabdus nematophila Insecticidal Activity

Casanova-Torres

Shokal

Morag

et al. 2017

Appl Environ Microbiol

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“…Little is known about the molecular mechanisms of action of dexamethasone in insects. Previous studies demonstrated that the immunosuppressive effect of dexamethasone in cellular immunity of insects depended on inhibition of phospholipase A 2 (PLA 2 ) and was reversed by administration of arachidonic acid (23,24,43). Nonetheless, similar to mammals, it is plausible that corticosteroids act by inhibiting multiple pathways of insect innate immunity.…”

Section: Discussionmentioning

confidence: 99%

Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis

Chamilos

Lewis

Hu³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

130

148

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Zygomycosis is an emerging frequently fatal opportunistic mycosis whose immunopathogenesis is poorly understood. We developed a zygomycosis model by injecting Drosophila melanogaster flies with a standardized amount of fungal spores from clinical Zygomycetes isolates to study virulence and host defense mechanisms. We found that, as opposed to most other fungi, which are nonpathogenic in D. melanogaster (e.g., Aspergillus fumigatus), Zygomycetes rapidly infect and kill wild-type flies. Toll-deficient flies exhibited increased susceptibility to Zygomycetes, whereas constitutive overexpression of the antifungal peptide Drosomycin in transgenic flies partially restored resistance to zygomycosis. D. melanogaster Schneider 2 phagocytic cells displayed decreased phagocytosis and caused less hyphal damage to Zygomycetes compared with that to A. fumigatus. Furthermore, phagocytosisdefective eater mutant flies displayed increased susceptibility to Zygomycetes infection. Classic enhancers of Zygomycetes virulence in humans, such as corticosteroids, increased iron supply, and iron availability through treatment with deferoxamine dramatically increased Zygomycetes pathogenicity in our model. In contrast, iron starvation induced by treatment with the iron chelator deferasirox significantly protected flies infected with Zygomycetes. Whole-genome expression profiling in wild-type flies after infection with Zygomycetes vs. A. fumigatus identified genes selectively down-regulated by Zygomycetes, which act in pathogen recognition, immune defense, stress response, detoxification, steroid metabolism, or tissue repair or have unknown functions. Our results provide insights into the factors that mediate hostpathogen interactions in zygomycosis and establish D. melanogaster as a promising model to study this important mycosis.animal models ͉ Rhizopus ͉ Toll receptor ͉ zygomycetes ͉ innate immunity F ungi of the class Zygomycetes, order Mucorales, are significant causes of life-threatening angioinvasive infections in patients with a wide range of immunosuppressive conditions and, occasionally, immunocompetent individuals (1, 2). Rhizopus species cause the majority of Zygomycetes infections, whereas Mucor, Rhizomucor, and Cunninghamella bertholletiae are less frequently encountered pathogens (1, 2). C. bertholletiae is considered the most pathogenic Zygomycetes species in humans (3).Once thought to be an uncommon infection, zygomycosis has recently emerged as the second most common opportunistic invasive mold infection after aspergillosis in patients with hematological malignancies and transplant recipients (2, 4-6). Zygomycosis has a particularly poor prognosis in these patients, with mortality rates Ͼ90% in disseminated infection (3,5,6).Quantitative and functional defects in immune effector cells associated with poorly controlled diabetes mellitus and receipt of corticosteroids or other immunosuppressive treatments are the principal predisposing factors for zygomycosis (1, 2). In addition, iron metabolism plays a central role in the p...

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“…Expression of the genes for these two proteins was induced by injecting the eicosanoid-precursor AA into silkworm larvae. With respect to a Drosophila model, Yajima et al (2003) showed that LPS-stimulated induction of the gene encoding the anti-bacterial protein, Diptericin, is mediated by the immunedeficiency (imd) pathway, but not by the Toll pathway. In a screen of inhibitory compounds, they also found that inhibitors of PLA 2 , including p-bromo-phenacyl bromide and dexamethasone, repressed LPS-stimulated gene expression.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandins A1 and E1 influence gene expression in an established insect cell line (BCIRL-HzAM1 cells)

Stanley

Goodman

et al. 2008

Insect Biochemistry and Molecular Biology

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Prostaglandins (PGs) and other eicosanoids exert important physiological actions in insects and other invertebrates, including influencing ion transport and mediating cellular immune defense functions. Although these actions are very well documented, we have no information on the mechanisms of PGs actions in insect cells. Here we report on the outcomes of experiments designed to test our hypothesis that PGs modulate gene expression in an insect cell line established from pupal ovarian tissue of the moth Helicoverpa zea (BCIRL-HzAM1 cells). We treated cells with either PGA 1 or PGE 1 for 12 or 24 h then analyzed cell lysates by 2-D electrophoresis. Analysis of the gels by densitometry revealed substantial changes in protein expression in some of the protein spots we analyzed. These spots were processed for mass spectrometric analysis by MALDI TOF/TOF, which yielded in silico protein identities for all 34 spots. The apparent changes in three of the proteins were confirmed by semi-quantative PCR, showing that the changes in mRNA expression were reflected in changes in protein expression. The 34 proteins were sorted into six categories, protein actions, lipid metabolism, signal transduction, protection, cell functions and metabolism. The findings support the hypothesis that one mechanism of PG action in insect cells is the modulation of gene expression. r

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A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A2-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity

Cited by 96 publications

References 33 publications

The Global Transcription Factor Lrp Is both Essential for and Inhibitory to Xenorhabdus nematophila Insecticidal Activity

The Global Transcription Factor Lrp Is both Essential for and Inhibitory to Xenorhabdus nematophila Insecticidal Activity

Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis

Prostaglandins A1 and E1 influence gene expression in an established insect cell line (BCIRL-HzAM1 cells)

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