Drosophila Immune Responses as Models for Human Immunity

Dushay, Mitchell S.; Eldon, Elizabeth D.

doi:10.1086/301694

Cited by 37 publications

(22 citation statements)

References 22 publications

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“…The mechanisms that regulate the different arms of insect immunity have been well investigated in Drosophila melanogaster (1). To combat microbial challenge, Drosophila relies on multiple defense reactions, which partly resemble the innate immune response of higher organisms (2)(3)(4)(5). Such a conserved innate immune pathway suggests ancient origin of immune response during metazoan evolution.…”

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confidence: 99%

Dynamic Repositioning of Dorsal to Two Different κB Motifs Controls Its Autoregulation during Immune Response in Drosophila

Mrinal¹,

Nagaraju

2010

Journal of Biological Chemistry

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Dynamic Repositioning of Dorsal to Two Different κB Motifs Controls Its Autoregulation during Immune Response in Drosophila

Mrinal¹,

Nagaraju

2010

Journal of Biological Chemistry

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“…Recently, an exciting approach has been to make use of the abilities of certain bacterial pathogens to infect nonmammalian model organisms with well-defined genetic systems, including the invertebrates Drosophila melanogaster (15,35,55) and Caenorhabditis elegans (14,42) and the plant Arabidopsis thaliana (52). This approach has been widely successful in identification of pathogen genes that support virulence (51) and host genes involved in sensing and clearing infections (50).…”

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confidence: 99%

Streptococcus-Zebrafish Model of Bacterial Pathogenesis

Neely¹,

Pfeifer

Caparon³

2002

Infect Immun

301

286

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Due to its small size, rapid generation time, powerful genetic systems, and genomic resources, the zebrafish has emerged as an important model of vertebrate development and human disease. Its well-developed adaptive and innate cellular immune systems make the zebrafish an ideal model for the study of infectious diseases. With a natural and important pathogen of fish, Streptococcus iniae, we have established a streptococcuszebrafish model of bacterial pathogenesis. Following injection into the dorsal muscle, zebrafish developed a lethal infection, with a 50% lethal dose of 10 3 CFU, and died within 2 to 3 days. The pathogenesis of infection resembled that of S. iniae in farmed fish populations and that of several important human streptococcal diseases and was characterized by an initial focal necrotic lesion that rapidly progressed to invasion of the pathogen into all major organ systems, including the brain. Zebrafish were also susceptible to infection by the human pathogen Streptococcus pyogenes. However, disease was characterized by a marked absence of inflammation, large numbers of extracellular streptococci in the dorsal muscle, and extensive myonecrosis that occurred far in advance of any systemic invasion. The genetic systems available for streptococci, including a novel method of mutagenesis which targets genes whose products are exported, were used to identify several mutants attenuated for virulence in zebrafish. This combination of a genetically amenable pathogen with a well-defined vertebrate host makes the streptococcus-zebrafish model of bacterial pathogenesis a powerful model for analysis of infectious disease.

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“…Dorsal controls cell fate along the dorsoventral axis of the embryo by activating and repressing an array of target genes (12,44). Dorsal and its vertebrate homolog NF-B also contribute to the innate immune response (14,18,21). In both insects and vertebrates, Toll family receptors mediate an immune response by triggering the degradation of IB or its Drosophila homolog Cactus, inhibitory factors that bind rel family proteins and block their nuclear translocation.…”

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Conjugation of Smt3 to Dorsal May Potentiate the Drosophila Immune Response

Bhaskar

Smith

Courey

2002

Molecular and Cellular Biology

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A variety of transcription factors are targets for conjugation to the ubiquitin-like protein Smt3 (also called SUMO). While many such factors exhibit enhanced activity under conditions that favor conjugation, the mechanisms behind this enhancement are largely unknown. We previously showed that the Drosophila melanogaster rel family factor, Dorsal, is a substrate for Smt3 conjugation. The conjugation machinery was found to enhance Dorsal activity at least in part by counteracting the Cactus-mediated inhibition of Dorsal nuclear localization. In this report, we show that Smt3 conjugation occurs at a single site in Dorsal (lysine 382), requires just the Smt3-activating and -conjugating enzymes, and is reversed by the deconjugating enzyme Ulp1. Mutagenesis of the acceptor lysine eliminates the response of Dorsal to the conjugation machinery and results in enhanced levels of synergistic transcriptional activation. Thus, in addition to controlling Dorsal localization, Smt3 also appears to regulate Dorsal-mediated activation, perhaps by modulating an interaction with a negatively acting nuclear factor. Finally, since Dorsal contributes to innate immunity, we examined the role of Smt3 conjugation in the immune response. We find that the conjugation machinery is required for lipopolysaccharide-induced expression of antimicrobial peptides in cultured cells and larvae, suggesting that Smt3 regulates Dorsal function in vivo.

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Drosophila Immune Responses as Models for Human Immunity

Cited by 37 publications

References 22 publications

Dynamic Repositioning of Dorsal to Two Different κB Motifs Controls Its Autoregulation during Immune Response in Drosophila

Dynamic Repositioning of Dorsal to Two Different κB Motifs Controls Its Autoregulation during Immune Response in Drosophila

Streptococcus-Zebrafish Model of Bacterial Pathogenesis

Conjugation of Smt3 to Dorsal May Potentiate the Drosophila Immune Response

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