• Proceedings of the Microbiological Society of Korea Conference
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• 2002.10a
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• pp.40-50
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• 2002

Fruit fly, Drosophila melanogaster has developed efficient immune mechanisms to prevent microbial infection, which are consisted of cellular and humoral responses. During the systemic or local infection, two distinct pathways (Toll and Imd) play major roles in antimicrobial peptide synthesis. The Toll pathway is required to defend Gram-positive bacterial and fungal infections, whereas the Imd pathway is important in Gram-negative bacterial infection. We have shown that the infection of the opportunistic Gram-negative bacterium, Pseudomonas aeruginosa strain PA14 (PA14) into fly dorsal thorax can kill the flies within 48 h ($100\%$ mortality) in our optimized infection condition, suggesting that the PA14 strain can cause disease progress in fly model system. We found that flies carrying a constitutively activated mutant form of the Toll receptor $(Tl^{10b})$ showed increased resistance to P. aeruginosa infection and that flies carrying mutations in the Toll signaling pathway as well as in the Imd signaling pathway was more susceptible to PA14 infection. All these results imply that the Toll pathway might be important in the resistance to this pathogenic Gram-negative bacterial infection.

• Molecules and Cells
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• v.46 no.10
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• pp.637-653
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• 2023

The physiology of most organisms, including Drosophila, is heavily influenced by their interactions with certain types of commensal bacteria. Acetobacter and Lactobacillus, two of the most representative Drosophila commensal bacteria, have stimulatory effects on host larval development and growth. However, how these effects are related to host immune activity remains largely unknown. Here, we show that the Drosophila development-promoting effects of commensal bacteria are suppressed by host immune activity. Mono-association of germ-free Drosophila larvae with Acetobacter pomorum stimulated larval development, which was accelerated when host immune deficiency (IMD) pathway genes were mutated. This phenomenon was not observed in the case of mono-association with Lactobacillus plantarum. Moreover, the mutation of Toll pathway, which constitutes the other branch of the Drosophila immune pathway, did not accelerate A. pomorum-stimulated larval development. The mechanism of action of the IMD pathway-dependent effects of A. pomorum did not appear to involve previously known host mechanisms and bacterial metabolites such as gut peptidase expression, acetic acid, and thiamine, but appeared to involve larval serum proteins. These findings may shed light on the interaction between the beneficial effects of commensal bacteria and host immune activity.

• BMB Reports
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• v.38 no.2
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• pp.121-127
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• 2005

Drosophila protects itself from infection by microbial organisms by means of its pivotal defense, the so-called innate immunity system. This is its sole defense as it lacks an adaptive immunity system such as is found in mammals. The strong conservation of innate immunity systems in organisms from Drosophila to mammals, and the ease with which Drosophila can be manipulated genetically, makes this fly a good model system for investigating the mechanisms of virulence of a number of medically important pathogens. Potentially damaging endogenous and/or exogenous challenges sensed by specific receptors initiate signals via the Toll and/or Imd signaling pathways. These in turn activate the transcription factors Dorsal, Dorsal-related immune factor (Dif) and Relish, culminating in transcription of genes involved in the production of antimicrobial peptides, melanization, phagocytosis, and the cytoskeletal rearrangement required for appropriate responses. Clarifying the regulatory interactions between the various pathways involved is very important for understanding the specificity and termination mechanism of the immune response.

• BMB Reports
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• v.41 no.4
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• pp.267-277
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• 2008

Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of anti-microbial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.