Host Immune Response and Differential Survival of the Sexes in Drosophila

Taylor, Katherine; Kimbrell, Deborah A.

doi:10.4161/fly.5082

Cited by 54 publications

(60 citation statements)

References 27 publications

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“…However, all three Imd alleles inhibit activation of the IIR by gram-negative bacteria (Taylor and Kimbrell 2007;Costa et al 2009). To determine whether effects on the expression of IIR genes are specific to the Imd pathway, we examined ATM 8 /+ and ATM 8 flies that carried a mutation in the Toll pathway gene Dif.…”

Section: Resultsmentioning

confidence: 99%

The Innate Immune Response Transcription Factor Relish Is Necessary for Neurodegeneration in aDrosophilaModel of Ataxia-Telangiectasia

2013

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Neurodegeneration is a hallmark of the human disease ataxia-telangiectasia (A-T) that is caused by mutation of the A-T mutated (ATM) gene. We have analyzed Drosophila melanogaster ATM mutants to determine the molecular mechanisms underlying neurodegeneration in A-T. Previously, we found that ATM mutants upregulate the expression of innate immune response (IIR) genes and undergo neurodegeneration in the central nervous system. Here, we present evidence that activation of the IIR is a cause of neurodegeneration in ATM mutants. Three lines of evidence indicate that ATM mutations cause neurodegeneration by activating the Nuclear Factor-kB (NF-kB) transcription factor Relish, a key regulator of the Immune deficiency (Imd) IIR signaling pathway. First, the level of upregulation of IIR genes, including Relish target genes, was directly correlated with the level of neurodegeneration in ATM mutants. Second, Relish mutations inhibited upregulation of IIR genes and neurodegeneration in ATM mutants. Third, overexpression of constitutively active Relish in glial cells activated the IIR and caused neurodegeneration. In contrast, we found that Imd and Dif mutations did not affect neurodegeneration in ATM mutants. Imd encodes an activator of Relish in the response to gram-negative bacteria, and Dif encodes an immune responsive NF-kB transcription factor in the Toll signaling pathway. These data indicate that the signal that causes neurodegeneration in ATM mutants activates a specific NF-kB protein and does so through an unknown activator. In summary, these findings suggest that neurodegeneration in human A-T is caused by activation of a specific NF-kB protein in glial cells.

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Section: Resultsmentioning

confidence: 99%

The Innate Immune Response Transcription Factor Relish Is Necessary for Neurodegeneration in aDrosophilaModel of Ataxia-Telangiectasia

2013

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“…Bacterial infections with E. coli ATCC 25922 were as previously described [65], [67]. A single spore isolate of Beauveria bassiana (strain GHA) was cultured on Sabouraud dextrose agar.…”

Section: Methodsmentioning

confidence: 99%

“…Spores were also flown on the space shuttle and we are happy to provide information upon request. Natural infection by B. bassiana used a dosage of 9.5×10 6 spores/fly, with procedures and survival assays as previously described [67]. Ten replicates of 20 flies each for all strains were used in all 3 experiments for the CARU hypergravity tests.…”

Section: Methodsmentioning

confidence: 99%

“…The centrifuge was stopped once per day to conduct survival counts. Control survival assays after bacterial and fungal infections on wild-type, hemolectin-Gal4; UAS-GFP, imd 1 , imd EY08573 and spz 4 [67] were conducted at Kennedy Space Center to establish that space and Earth fly infections were proceeding in accordance with our standardized conditions.…”

Section: Methodsmentioning

confidence: 99%

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Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila

et al. 2014

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Space travel presents unlimited opportunities for exploration and discovery, but requires better understanding of the biological consequences of long-term exposure to spaceflight. Immune function in particular is relevant for space travel. Human immune responses are weakened in space, with increased vulnerability to opportunistic infections and immune-related conditions. In addition, microorganisms can become more virulent in space, causing further challenges to health. To understand these issues better and to contribute to design of effective countermeasures, we used the Drosophila model of innate immunity to study immune responses in both hypergravity and spaceflight. Focusing on infections mediated through the conserved Toll and Imd signaling pathways, we found that hypergravity improves resistance to Toll-mediated fungal infections except in a known gravitaxis mutant of the yuri gagarin gene. These results led to the first spaceflight project on Drosophila immunity, in which flies that developed to adulthood in microgravity were assessed for immune responses by transcription profiling on return to Earth. Spaceflight alone altered transcription, producing activation of the heat shock stress system. Space flies subsequently infected by fungus failed to activate the Toll pathway. In contrast, bacterial infection produced normal activation of the Imd pathway. We speculate on possible linkage between functional Toll signaling and the heat shock chaperone system. Our major findings are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related transcriptional responses and results in a specific inability to mount a Toll-mediated infection response.

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“…In humans, a difference between the sexes in the numbers of blood cell types is well established, but the effects are unclear (Blum and Pabst 2007; Huppert et al 1998; Reichert et al 1991). In both humans and Drosophila , there are differences in the immune responses between the sexes that affect health (Dale et al 2006; Marriott and Huet-Hudson 2006; Shames 2002; Taylor and Kimbrell 2007; Ye et al 2009; Zandman-Goddard et al 2007), and the blood cell number differential may be part of mediating the immune response differences. Recently, Drosophila hemocytes have been shown to directly signal immune induction of the fat body, and a reduced number of hemocytes resulted in less immune induction (Shia et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Hemocytes in Drosophila Requires dappled Cytochrome b5

et al. 2011

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A major category of mutant hematopoietic phenotypes in Drosophila is melanotic tumors or nodules, which consist of abnormal and overproliferated blood cells, similar to granulomas. Our analyses of the melanotic mutant dappled have revealed a novel type of gene involved in blood cell regulation. The dappled gene is an essential gene that encodes cytochrome b5, a conserved hemoprotein that participates in electron transfer in multiple biochemical reactions and pathways. Viable mutations of dappled cause melanotic nodules and hemocyte misregulation during both hematopoietic waves of development. The sexes are similarly affected, but hemocyte number is different in females and males of both mutants and wild type. Additionally, initial tests show that curcumin enhances the dappled melanotic phenotype and establish screening of endogenous and xenobiotic compounds as a route for analysis of cytochrome b5 function. Overall, dappled provides a tractable genetic model for cytochrome b5, which has been difficult to study in higher organisms.

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Host Immune Response and Differential Survival of the Sexes in Drosophila

Cited by 54 publications

References 27 publications

The Innate Immune Response Transcription Factor Relish Is Necessary for Neurodegeneration in aDrosophilaModel of Ataxia-Telangiectasia

The Innate Immune Response Transcription Factor Relish Is Necessary for Neurodegeneration in aDrosophilaModel of Ataxia-Telangiectasia

Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila

Regulation of Hemocytes in Drosophila Requires dappled Cytochrome b5

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