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Drosophila immunity

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https://www.readbyqxmd.com/read/28426766/activated-entomopathogenic-nematode-infective-juveniles-release-lethal-venom-proteins
#1
Dihong Lu, Marissa Macchietto, Dennis Chang, Mirayana M Barros, James Baldwin, Ali Mortazavi, Adler R Dillman
Entomopathogenic nematodes (EPNs) are unique parasites due to their symbiosis with entomopathogenic bacteria and their ability to kill insect hosts quickly after infection. It is widely believed that EPNs rely on their bacterial partners for killing hosts. Here we disproved this theory by demonstrating that the in vitro activated infective juveniles (IJs) of Steinernema carpocapsae (a well-studied EPN species) release venom proteins that are lethal to several insects including Drosophila melanogaster. We confirmed that the in vitro activation is a good approximation of the in vivo process by comparing the transcriptomes of individual in vitro and in vivo activated IJs...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28425174/costs-and-benefits-of-sub-lethal-drosophila-c-virus-infection
#2
Vanika Gupta, Charlotte Stewart, Samuel S C Rund, Katy Monteith, Pedro F Vale
Viruses are major evolutionary drivers of insect immune systems. Much of our knowledge of insect immune responses derives from experimental infections using the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal pathogen doses through septic injury, frequently overwhelming host physiology. While this approach has revealed several immune mechanisms, it is less informative about the fitness costs hosts may experience during infection in the wild. Using both systemic and oral infection routes we find that even apparently benign, sub-lethal infections with the horizontally transmitted Drosophila C Virus (DCV) can cause significant physiological and behavioral morbidity that is relevant for host fitness...
April 20, 2017: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/28418397/bap180-baf180-is-required-to-maintain-homeostasis-of-intestinal-innate-immune-response-in-drosophila-and-mice
#3
Xiaomeng He, Junjing Yu, Min Wang, Yang Cheng, Yanan Han, Shuo Yang, Guizhi Shi, Lei Sun, Ying Fang, Si-Tang Gong, Zhong Wang, Yang-Xin Fu, Lei Pan, Hong Tang
Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload...
April 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28418029/tmcactin-plays-an-important-role-in-gram-negative-and-positive-bacterial-infection-by-regulating-expression-of-7-amp-genes-in-tenebrio-molitor
#4
Yong Hun Jo, Yu Jung Kim, Ki Beom Park, Jeong Hwan Seong, Soo Gon Kim, Soyi Park, Mi Young Noh, Yong Seok Lee, Yeon Soo Han
Cactin was originally identified as an interactor of the Drosophila IκB factor Cactus and shown to play a role in controlling embryonic polarity and regulating the NF-κB signaling pathway. While subsequent studies have identified the roles for Cactin in the mammalian immune response, the immune function of Cactin in insects has not been described yet. Here, we identified a Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and characterized its functional role in innate immunity. TmCactin was highly expressed in prepupa to last instar stages, and its expression was high in the integument and Malpighian tubules of last instar larvae and adults...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28413160/interaction-between-familial-transmission-and-a-constitutively-active-immune-system-shapes-gut-microbiota-in-drosophila-melanogaster
#5
Rupal Mistry, Ilias Kounatidis, Petros Ligoxygakis
Resident gut bacteria are constantly influencing the immune system. Yet the role of the immune system in shaping microbiota composition during an organism's lifespan has remained unclear. Experiments in mice have been inconclusive due to differences in husbandry schemes that led to conflicting results. We used Drosophila as a genetically tractable system with simpler gut bacterial population structure and streamlined genetic backgrounds and established cross schemes to address this issue. We found that depending on their genetic background, young flies had microbiota of different diversities that converged with age to the same Acetobacteraceae-dominated pattern in healthy flies...
April 16, 2017: Genetics
https://www.readbyqxmd.com/read/28411220/the-global-transcription-factor-lrp-is-both-essential-for-and-inhibitory-to-xenorhabdus-nematophila-insecticidal-activity
#6
Ángel M Casanova-Torres, Upasana Shokal, Neta Morag, Ioannis Eleftherianos, Heidi Goodrich-Blair
In the entomopathogenic bacterium Xenorhabdus nematophila, cell-to-cell 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 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...
April 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28411188/raf-kinase-inhibitor-protein-preferentially-promotes-tlr3-triggered-signaling-and-inflammation
#7
Rongrong Lai, Meidi Gu, Wei Jiang, Wenlong Lin, Penglei Xu, Zhiyong Liu, He Huang, Huazhang An, Xiaojian Wang
Raf kinase inhibitor protein (RKIP) protects against host immunological responses in nematodes and Drosophila Whether RKIP functions in innate immune responses in mammals remains unknown. In this article, we report that RKIP preferentially regulates the TLR3-mediated immune response in macrophages. RKIP deficiency or silencing significantly decreases polyinosinic:polycytidylic acid [Poly(I:C)]-induced IFN-β, IL-6, and TNF-α production without affecting the counterpart induced by LPS or CpG. Compared with their wild-type counterparts, RKIP-deficient mice produce less IFN-β, IL-6, and TNF-α in serum and display decreased lethality upon peritoneal Poly(I:C) plus d-galactosamine injection...
April 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28409340/drosophila-malpighian-tubules-a-model-for-understanding-kidney-development-function-and-disease
#8
Naveen Kumar Gautam, Puja Verma, Madhu G Tapadia
The Malpighian tubules of insects are structurally simple but functionally important organs, and their integrity is important for the normal excretory process. They are functional analogs of human kidneys which are important physiological organs as they maintain water and electrolyte balance in the blood and simultaneously help the body to get rid of waste and toxic products after various metabolic activities. In addition, it receives early indications of insults to the body such as immune challenge and other toxic components and is essential for sustaining life...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28404605/proteomics-analysis-identifies-orthologs-of-human-chitinase-like-proteins-as-inducers-of-tube-morphogenesis-defects-in-drosophila
#9
Sandra G Zimmerman, Gennifer E Merrihew, Michael J MacCoss, Celeste A Berg
Elevated levels of human chitinase-like proteins (CLPs) are associated with numerous chronic inflammatory diseases and several cancers, often correlating with poor prognosis. Nevertheless, there is scant knowledge of their function. The CLPs normally mediate immune responses and wound healing, and when upregulated, they can promote disease progression by remodeling tissue, activating signaling cascades, stimulating proliferation and migration, and by regulating adhesion. We identified Imaginal disc growth factors (Idgfs), orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis designed to discover factors that regulate tube morphogenesis in a Drosophila melanogaster model of tube formation...
April 12, 2017: Genetics
https://www.readbyqxmd.com/read/28388413/circulating-immune-cells-mediate-a-systemic-rnai-based-adaptive-antiviral-response-in-drosophila
#10
Michel Tassetto, Mark Kunitomi, Raul Andino
Effective antiviral protection in multicellular organisms relies on both cell-autonomous and systemic immunity. Systemic immunity mediates the spread of antiviral signals from infection sites to distant uninfected tissues. In arthropods, RNA interference (RNAi) is responsible for antiviral defense. Here, we show that flies have a sophisticated systemic RNAi-based immunity mediated by macrophage-like haemocytes. Haemocytes take up dsRNA from infected cells and, through endogenous transposon reverse transcriptases, produce virus-derived complementary DNAs (vDNA)...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28377500/innate-immune-signaling-in-drosophila-is-regulated-by-tgf%C3%AE-activated-kinase-tak1-triggered-ubiquitin-editing
#11
Li Chen, Nicholas Paquette, Shahan Mamoor, Florentina Rus, Anubhab Nandy, John Leszyk, Scott A Shaffer, Neal Silverman
Coordinated regulation of innate immune responses is necessary in all metazoans. In Drosophila, the Imd pathway detects gram-negative bacterial infections through recognition of DAP-type peptidoglycan and activation of the NF-κB precursor Relish, which drives robust antimicrobial peptide (AMP) gene expression. Imd is a receptor-proximal adaptor protein homologous to mammalian RIP1 that is regulated by proteolytic cleavage and K63-polyubiquitination. However, the precise events and molecular mechanisms that control the post-translational modification of Imd remain unclear...
April 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28346426/mrl-proteins-cooperate-with-activated-ras-in-glia-to-drive-distinct-oncogenic-outcomes
#12
E Taylor, N Alqadri, L Dodgson, D Mason, E Lyulcheva, G Messina, D Bennett
The Mig10/RIAM/Lpd (MRL) adapter protein Lpd regulates actin dynamics through interactions with Scar/WAVE and Ena/VASP proteins to promote the formation of cellular protrusions and to stimulate invasive migration. However, the ability of MRL proteins to interact with multiple actin regulators and to promote serum response factor (SRF) signalling has raised the question of whether MRL proteins employ alternative downstream mechanisms to drive oncogenic processes in a context-dependent manner. Here, using a Drosophila model, we show that overexpression of either human Lpd or its Drosophila orthologue Pico can promote growth and invasion of Ras(V12)-induced cell tumours in the brain...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28342875/the-nociception-genes-painless-and-piezo-are-required-for-the-cellular-immune-response-of-drosophila-larvae-to-wasp-parasitization
#13
Yumiko Tokusumi, Tsuyoshi Tokusumi, Robert A Schulz
In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28325838/signaling-pathway-for-phagocyte-priming-upon-encounter-with-apoptotic-cells
#14
Saori Nonaka, Yuki Ando, Takuto Kanetani, Chiharu Hoshi, Yuji Nakai, Firzan Nainu, Kaz Nagaosa, Akiko Shiratsuchi, Yoshinobu Nakanishi
The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28318765/in-vivo-electroporation-in-dna-vlp-prime-boost-preferentially-enhances-hiv-1-envelope-specific-igg2a-neutralizing-antibody-and-cd8-t-cell-responses
#15
Xun Huang, Qianqian Zhu, Xiaoxing Huang, Lifei Yang, Yufeng Song, Ping Zhu, Paul Zhou
Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28273919/differential-modulation-of-the-cellular-and-humoral-immune-responses-in-drosophila-is-mediated-by-the-endosomal-arf1-asrij-axis
#16
Rohan J Khadilkar, Arindam Ray, D R Chetan, Arghyashree RoyChowdhury Sinha, Srivathsa S Magadi, Vani Kulkarni, Maneesha S Inamdar
How multicellular organisms maintain immune homeostasis across various organs and cell types is an outstanding question in immune biology and cell signaling. In Drosophila, blood cells (hemocytes) respond to local and systemic cues to mount an immune response. While endosomal regulation of Drosophila hematopoiesis is reported, the role of endosomal proteins in cellular and humoral immunity is not well-studied. Here we demonstrate a functional role for endosomal proteins in immune homeostasis. We show that the ubiquitous trafficking protein ADP Ribosylation Factor 1 (ARF1) and the hemocyte-specific endosomal regulator Asrij differentially regulate humoral immunity...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271570/single-domain-antibodies-for-the-knockdown-of-cytosolic-and-nuclear-proteins
#17
REVIEW
Thomas Böldicke
Single domain antibodies (sdAbs) from camels or sharks comprise only the variable heavy chain domain. Human sdAbs comprise the variable domain of the heavy chain (VH) or light chain (VL) and can be selected from human antibodies. SdAbs are stable, non aggregating molecules in vitro and in vivo compared to complete antibodies and scFv fragments. They are excellent novel inhibitors of cytosolic/nuclear proteins because they are correctly folded inside the cytosol in contrast to scFv fragments. SdAbs are unique because of their excellent specificity and possibility to target posttranslational modifications such as phosphorylation sites, conformers or interaction regions of proteins that cannot be targeted with genetic knockout techniques and are impossible to knockdown with RNAi...
March 8, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28264763/peptidoglycan-sensing-by-octopaminergic-neurons-modulates-drosophila-oviposition
#18
C Leopold Kurz, Bernard Charroux, Delphine Chaduli, Annelise Viallat-Lieutaud, Julien Royet
As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection, animals can engage in behaviors that lower the impact of the infection. The molecular mechanisms by which microbes impact host behavior are not well understood. We demonstrate that bacterial infection of Drosophila females reduces oviposition and that peptidoglycan, the component that activates Drosophila antibacterial response, is also the elicitor of this behavioral change...
March 7, 2017: ELife
https://www.readbyqxmd.com/read/28262681/regulation-of-phagocyte-triglyceride-by-a-stat-atg2-pathway-controls-mycobacterial-infection
#19
Claire B Péan, Mark Schiebler, Sharon W S Tan, Jessica A Sharrock, Katrin Kierdorf, Karen P Brown, M Charlotte Maserumule, Shinelle Menezes, Martina Pilátová, Kévin Bronda, Pierre Guermonprez, Brian M Stramer, R Andres Floto, Marc S Dionne
Mycobacterium tuberculosis remains a global threat to human health, yet the molecular mechanisms regulating immunity remain poorly understood. Cytokines can promote or inhibit mycobacterial survival inside macrophages and the underlying mechanisms represent potential targets for host-directed therapies. Here we show that cytokine-STAT signalling promotes mycobacterial survival within macrophages by deregulating lipid droplets via ATG2 repression. In Drosophila infected with Mycobacterium marinum, mycobacterium-induced STAT activity triggered by unpaired-family cytokines reduces Atg2 expression, permitting deregulation of lipid droplets...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28258224/transglutaminase-catalyzed-incorporation-of-polyamines-masks-the-dna-binding-region-of-the-transcription-factor-relish
#20
Kouki Maki, Toshio Shibata, Shun-Ichiro Kawabata
In Drosophila, the final immune deficiency (IMD) pathway-dependent signal is transmitted through proteolytic conversion of the nuclear factor-κB (NF-κB)-like transcription factor Relish to the active N-terminal fragment Relish-N. Relish-N is then translocated from the cytosol into the nucleus for the expression of IMD-controlled genes. We previously demonstrated that transglutaminase (TG) suppresses the IMD pathway by polymerizing Relish-N to inhibit its nuclear translocation. Conversely, we also demonstrated that orally ingested synthetic amines, such as monodansylcadaverine (DCA) and biotin-labeled pentylamine, are TG-dependently incorporated into Relish-N, causing the nuclear translocation of modified Relish-N in gut epithelial cells...
April 14, 2017: Journal of Biological Chemistry
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