A Specific Primed Immune Response in Drosophila Is Dependent on Phagocytes

Department of Microbiology and Immunology, Stanford University, Stanford, California, United States of America.
PLoS Pathogens (Impact Factor: 7.56). 04/2007; 3(3):e26. DOI: 10.1371/journal.ppat.0030026
Source: PubMed


Author Summary

Due to the common practice of vaccination and prominence of AIDS, people are already aware of the distinction between adaptive and innate immunity without realizing it. All organisms have an innate immune response, but only vertebrates possess T cells and the ability to produce antibodies. It has been a long-standing assumption that invertebrate immune systems are not adaptive and respond identically to multiple challenges. In this study, we demonstrate that the fly innate immune response adapts to repeated challenges; flies preinoculated with dead Streptococcus pneumoniae are protected against a second, otherwise-lethal dose. Although the underlying mechanisms are likely to be very different, this primed response is reminiscent to vaccine-induced protection in that it exhibits coarse specificity (dead S. pneumoniae only protects against itself), persists for the life of the fly and is dependent on phagocytic cells. This result prompts the obvious question of whether the innate immune system of vertebrates shares a similar biology. Such a finding is of particular interest since immunocompromised individuals only possess an innate immune system.

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    • "b There was no difference in the expression of Glut-1 and Glut-3 by 168 h between sham and infected with antibiotics flies recovery from sepsis. Our model that mimics the recently described persistent inflammation , immunosuppression, and catabolic syndrome (PICS) observed in survivors of sepsis, however, has provided more unresolved questions if not some limitations[19,35]. First, we did not measure the caloric intake in Drosophila; however, they had similar weights by 1 week. "
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    ABSTRACT: Multiple organ failure, wasting, increased morbidity, and mortality following acute illness complicates the health span of patients surviving sepsis. Persistent inflammation has been implicated, and it is proposed that insulin signaling contributes to persistent inflammatory signaling during the recovery phase after sepsis. However, mechanisms are unknown and suitable pre-clinical models are lacking. We therefore developed a novel Drosophila melanogaster model of sepsis to recapitulate the clinical course of sepsis, explored inflammation over time, and its relation to impaired mobility, metabolic disturbance, and changes in lifespan. We used wild-type (WT), Drosomycin-green fluorescent protein (GFP), and NF-κB-luc reporter male Drosophila melanogaster 4–5 days of age (unmanipulated). We infected Drosophila with Staphylococcus aureus (infected without treatment) or pricked with aseptic needles (sham). Subsets of insects were treated with oral linezolid after the infection (infected with antibiotics). We assessed rapid iterative negative geotaxis (RING) in all the groups as a surrogate for neuromuscular functional outcome up to 96 h following infection. We harvested the flies over the 7-day course to evaluate bacterial burden, inflammatory and metabolic pathway gene expression patterns, NF-κB translation, and metabolic reserve. We also followed the lifespan of the flies. Our results showed that when treated with antibiotics, flies had improved survival compared to infected without treatment flies in the early phase of sepsis up to 1 week (81 %, p = 0.001). However, the lifespan of infected with antibiotics flies was significantly shorter than that of sham controls (p = 0.001). Among infected with antibiotic sepsis survivors, we observed persistent elevation of NF-κB in the absence of any obvious infection as shown by culturing flies surviving sepsis. In the same group, geotaxis had an early (18 h) and sustained decline compared to its baseline. Geotaxis in infected with antibiotics sepsis survivors was significantly lower than that in sham and age-matched unmanipulated flies at 18 and 48 h. Expression of antimicrobial peptides (AMP) remained significantly elevated over the course of 7 days after sepsis, especially drosomycin (5.7-fold, p = 0.0145) on day 7 compared to that of sham flies. Infected with antibiotics flies had a trend towards decreased Akt activation, yet their glucose stores were significantly lower than those of sham flies (p = 0.001). Sepsis survivors had increased lactate levels and LDH activity by 1 week, whereas ATP and pyruvate content was similar to that of the sham group. In summary, our model mimics human survivors of sepsis with persistent inflammation, impaired motility, dysregulated glucose metabolism, and shortened lifespan.
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    • "This may hold special relevance for newly described, somewhat controversial phenomena such as invertebrate immune priming. Priming enhances the probability of host survival upon repeated exposure to microbes and is thought to often be mediated by hemocytes (Pham et al. 2007), which are under delayed DI. However, immune priming also suffers from repeatability issues and shows inconsistent penetrance across developmental stages (Trauer and Hilker 2013), consistent with DI effects. "
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    Full-text · Article · Nov 2015 · The American Naturalist
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    • "Thus, T. ni are unlikely to encounter an abundance of these bacteria on their host plants; thus it might be possible that their response will be different to unfamiliar contaminants. Different bacterial species probably elicit different responses, exemplified by the fact that immune priming can be specific to the taxonomic type, species or strain of pathogens (Sadd & Schmid-Hempel, 2006; Pham et al., 2007; Roth et al., 2009). We used two Gram-negative bacteria belonging to the same genus, whereas Freitak et al. (2007) used both Gram-negative and positive bacteria of differing genera. "
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