InteractiveFly: GeneBrief

Drosocin: Biological Overview | References

Gene name - Drosocin

Synonyms -

Cytological map position - 51C1-51C1

Function - secreted antibacterial peptide

Keywords - an o-Glycosylated antibacterial peptide with activity against Gram-negative and Gram-positive bacteria. It is expressed in the fat body during the systemic immune response and is expressed in various epithelia. The expression of Dro is regulated at the transcriptional level mostly by the immune deficiency pathway - hemocytes relay an innate immune response to the blood cell reservoir: through Imd signaling and the Jak/Stat pathway ligand Upd3, hemocytes act as sentinels of bacterial infection, inducing expression of the antimicrobial peptide Drosocin in respiratory epithelia and colocalizing fat body domains

Symbol - Dro

FlyBase ID: FBgn0010388

Genetic map position - chr2R:14,745,961-14,746,714

NCBI classification - antibacterial peptide

Cellular location - secreted

NCBI links: EntrezGene, Nucleotide, Protein

Drosocin orthologs: Biolitmine

The use of adult Drosophila melanogaster as a model for hematopoiesis or organismal immunity has been debated. Addressing this question, an extensive reservoir of blood cells (hemocytes) was identified at the respiratory epithelia (tracheal air sacs) of the thorax and head. Lineage tracing and functional analyses demonstrate that the majority of adult hemocytes are phagocytic macrophages (plasmatocytes) from the embryonic lineage that parallels vertebrate tissue macrophages. Surprisingly, no sign of adult hemocyte expansion was observed. Instead, hemocytes play a role in relaying an innate immune response to the blood cell reservoir: through Imd signaling and the Jak/Stat pathway ligand Upd3, hemocytes act as sentinels of bacterial infection, inducing expression of the antimicrobial peptide Drosocin in respiratory epithelia and colocalizing fat body domains. Drosocin expression in turn promotes animal survival after infection. This work identifies a multi-signal relay of organismal humoral immunity, establishing adult Drosophila as model for inter-organ immunity (Sanchez Bosch, 2019).

Drosophila melanogaster has greatly promoted understanding of innate immunity and blood cell development, but the capacity of the adult animal as a model remains a matter of debate. Most studies reported lack of new blood cell production and increasing immunosenescence, while one publication claimed continued hematopoietic activity in adult Drosophila (Sanchez Bosch, 2019).

Drosophila blood cells, or hemocytes, emerge from two lineages that persist into the adult, showing parallels with the two myeloid systems in vertebrates. First, hemocytes originating in the embryo parallel vertebrate tissue macrophages, as they quickly differentiate into plasmatocytes (macrophage-like cells), and subsequently proliferate extensively, mainly in the hematopoietic pockets (HPs) of the larva (Gold, 2014; Gold, 2015; Makhijani, 2011; Makhijani, 2012). At least some of these plasmatocytes can further differentiate into other blood cell types such as crystal cells and, under immune challenge, lamellocytes. Second, hemocytes originating in the lymph gland (LG) also give rise to plasmatocytes, crystal cells, and lamellocytes, yet in the lymph gland they are predominantly generated from blood cell progenitors (prohemocytes). At the beginning of metamorphosis, hemocytes from both the hematopoietic pockets and the lymph gland enter the open circulatory system and intermix. The subsequent fate and capacity of adult blood cells has remained largely unclear. Accordingly, this study comprehensively investigated the hematopoietic capacity of the blood cell system in adult Drosophila. A second part of this study focused on the role of adult blood cells in the humoral immune response, identifying a system of organismal innate immunity that centers on the respiratory epithelia in Drosophila (Sanchez Bosch, 2019).

Historically, Drosophila has been instrumental in the discovery of innate immunity and Toll like receptor (TLR) signaling. Toll and the related immune deficiency (Imd) signaling are evolutionary conserved NFκB family pathways, studied in detail regarding their upstream activation by pathogens and other inputs, and downstream signal transduction components and mechanisms. Targets include antimicrobial peptides (AMPs), which have been investigated for their transcriptional gene regulation and functional properties. TLR signaling has been well established also in vertebrate systems for its roles in infection and inflammation. However, it has been far less understood how multiple tissues or organs communicate with each other to elicit local innate immune responses (Sanchez Bosch, 2019).

Addressing these questions, this study clarifies basic principles of the blood cell system in adult Drosophila and its role in multi-tissue organismal immunity. An extensive blood cell reservoir was identified at the respiratory epithelia and fat body, its dynamics were investigated and probed for various signs of hematopoiesis. A key role of adult blood cells is demonstrated as sentinels of bacterial infection that trigger a humoral response in their reservoir, i.e., the respiratory epithelia and colocalizing domains of the fat body. This response culminates in the expression of the AMP gene Drosocin, which is shown to be significant for animal survival after bacterial infection. This work identifies Imd signaling and Upd3 expression in hemocytes as required steps in this relay of organismal immunity, laying the foundation for the use of adult Drosophila to dissect additional mechanisms of multi-tissue innate immunity in the future (Sanchez Bosch, 2019).

This study discovered a central role for an extensive blood cell reservoir at the respiratory epithelia and fat body of adult Drosophila. The reservoir serves as major receptacle of blood cells and foreign particles, and in addition executes a local humoral immune response of Drosocin expression that promotes animal survival after bacterial infection. Both functions are tied together by hemocytes acting as sentinels of infection, that signal through the Imd pathway and Upd3 to induce Drosocin expression in the tissues of their surrounding reservoir, i.e., the respiratory epithelia and colocalizing domains of the fat body (Sanchez Bosch, 2019).

Historic literature on Drosophila and other insects focused on the adult heart as the site of hemocyte accumulation. It described clusters of hemocytes at the ostia of the heart as 'immune organ', locations where hemocytes and bacteria accumulate. More recently, adult blood cell production at the heart was proposed (Ghosh, 2015). Some studies described functions of hemocytes in other locations, such as at the ovaries or along the gut of adult flies. Taking a more global cryosectioning approach afforded the identification of the largest reservoir of hemocytes in adult Drosophila, which surrounds the respiratory epithelia and is lined by fat body of the thorax and head. It is concluded that hemocytes and particles are delivered to these areas by the streaming hemolymph, even though the detailed anatomy of the open circulatory system remains to be mapped in more detail. Hemocytes may be physically caught in these locations, or in addition may engage in active adhesion. The intimate relationship of hemocytes with the respiratory epithelia, hemolymph, and adjacent fat body may serve interconnected roles, (1) guarding the respiratory epithelia as a barrier to the environment through functions of hemocytes in both phagocytosis and the induction of humoral immunity, and (2) facilitating gas exchange of hemocytes and nearby immune tissues, which in turn may again benefit defense functions. The former may be particularly advantageous in the defense against fungal pathogens that invade Drosophila via the tracheal system as primary route of infection, such as the entomopathogenic fungus B. bassiana. Regarding the latter, a study in caterpillars described the association of hemocytes with trachea, proposing a function for the respiratory system to supply hemocytes with oxygen (Sanchez Bosch, 2019).

Drosophila adult blood cells derive from two lineages: one that originates in the embryo and resembles vertebrate tissue macrophages, and another that produces blood cells in the lymph gland through a progenitor-based mechanism. It is estimated that more than 60% of adult hemocytes derive from the embryonic lineage is surprising, considering past views that the majority of adult hemocytes would derive from the lymph gland. It places more importance on the Drosophila embryonic lineage of hemocytes and suggests additional parallels with tissue macrophages in vertebrates, which persist into adulthood and form a separate myeloid system independent of the progenitor-derived monocyte lineage. Future research will show whether the relative contribution of the two hemocyte lineages to the adult blood cell pool will be the same or different under conditions of stress and immune challenges (Sanchez Bosch, 2019).

Given that embryonic-lineage plasmatocytes are highly proliferative in the hematopoietic pockets of the larva, and lymph gland hemocyte progenitors and some lymph gland plasmatocytes proliferate during larval development, the absence of hemocyte proliferation in the adult may be surprising. Nevertheless, combining the broad evidence supporting lack of significant hematopoietic activity in adult Drosophila, and evidence that Srp in adult Drosophila is not a progenitor marker, the findings robustly contradict an adult hematopoiesis model. The findings further reveal important differences to embryonic development, where Srp is required for the specification of undifferentiated prohemocytes. This study shows that during maturation of the adult animal, hemocytes relocate to the respiratory epithelia and the heart, upon completion of cytolysis of larval fat body cells, thereby refuting claims of new blood cell production at the heart. Similarly, seemingly increased numbers of fluorescently labeled hemocytes following bacterial infection are likely based on infection-induced upregulation of hemocyte-specific genes and their respective enhancers including the reporter HmlΔ-GAL4, UAS-GFP. Enhanced hemocyte expression of Hemolectin (Hml) and other hemocyte-specific markers post-infection has been described previously (Sanchez Bosch, 2019).

Taken together, this broad evidence speaks to a lack of significant hematopoietic capacity of the blood cell system in adult Drosophila. The findings are in agreement with other studies that have reported a lack of hemocyte proliferation in adult Drosophila and functional immunosenescence in aging flies. Despite the scope of conditions tested, the possibility cannot be excluded that some other specific immune challenge or stress might exist that would be potent enough to trigger proliferation- or differentiation-based blood cell production in adult Drosophila. Likewise, it cannot be excluded that adult Drosophila may possess small numbers of proliferation- and/or differentiation-competent progenitors that may have persisted e.g. from the lymph gland posterior lobes; such cells might give rise to new differentiated hemocytes, although according to the current data they would remain insignificant in number (Sanchez Bosch, 2019).

Taking into account the short reproductive phase and relatively short life span of Drosophila, the adult fly may be sufficiently equipped with the pool of hemocytes that is produced in the embryo and larva. In fact, hemocytes do not seem essential for the immediate survival of adult flies: Drosophila ablated of hemocytes, and mutants devoid of hemocytes, survive to adulthood although they are more prone to, and succumb more rapidly to infection. A model is proposed that places emphasis on larval development as the sensitive phase for the expansion and regulation of the adult blood cell pool. In the larva, hemocytes of both the embryonic and lymph gland lineage integrate signals from a variety of internal and external stimuli to adapt to existing life conditions (Sanchez Bosch, 2019).

This work reveals a role for hemocytes in a local humoral immune response of the fat body and respiratory epithelia. Previous studies on hemocyte-ablated flies have reported increases in Defensin and IM1 expression. In contrast, this study finds a positive role for hemocytes in the induction of Drosocin in tissues that form the hemocyte reservoir, i.e., the respiratory epithelia and fat body domains of the head and thorax. The concept of hemocytes promoting AMP expression in other tissues is well established. A role for AMP expression in surface epithelia that interface with the environment was reported in a previous study, and Drosocin expression was described in embryonic and larval trachea and the abdominal tracheal trunks of adult Drosophila, albeit not in the respiratory epithelia (Sanchez Bosch, 2019).

In adult Drosophila, hemocytes tightly localize between the respiratory epithelia and fat body tissue that occupies the space toward to the cuticle exoskeleton. It is proposed that this close anatomical relationship facilitates rapid local signaling. Consistent with previous knowledge that Drosocin expression is lost in imd mutant backgrounds, this study found that hemocyte-autonomous Imd signaling is required, albeit not sufficient, to trigger the infection-induced Drosocin response. Likewise, the Imd pathway upstream receptor PGRP-LC is required in hemocytes, suggesting that DAP-type peptidoglycan recognition and initiation of Imd signaling are a critical step in triggering the Drosocin response. Transcriptional induction of upd3 by Imd signaling is supported by putative Rel binding sites identified in the upd3 genomic region, two of which are even fully conserved across seven Drosophilids including Drosophila melanogaster. The data suggest roles for hemocyte-expressed upd3, and corresponding Jak/Stat signaling in cells of the fat body and respiratory system, all of which are required albeit not sufficient. Overactivation of the pathway paradoxically suppresses Drosocin expression, and even temporally restricted expression of activated hopTumL in trachea was largely lethal, possibly indicating leaky expression of the transgene. Overall, it can only be speculated that the unexpected effects of Jak/Stat overactivation might be due to activation of some negative feedback loop or other complex signaling changes that remain a matter of future investigation (Sanchez Bosch, 2019).

Several reports provide precedent for a role of hemocyte-expressed Upd3 in the induction of immune responses in other target tissues. Following septic injury, upregulation of upd3 in hemocytes triggers induction of stress peptide genes of the turandot family including totA in fat body. Similarly, in response to injury, hemocyte-produced Upd3 induces Jak/Stat signaling in the fat body and gut. Under lipid-rich diet, upd3 is induced in hemocytes, causing impaired glucose homeostasis and reduced lifespan in adult Drosophila. In the larva, hemocyte-derived Upd2 and -3 activate Jak/Stat signaling in muscle, which are required for the immune response against parasitic wasps. However, in the Drosocin response around the reservoir of hemocytes, the data predict that additional signal/s and/or signaling pathway/s are needed to initiate Drosocin expression and potentially restrict its expression to defined fat body domains of the head and thorax. Additional events may include signaling through Toll or other signaling pathways in hemocytes and/or other tissues including the respiratory epithelia and fat body. Likewise, other types of signals may be required, such as reactive oxygen species (ROS) or nitric oxide (NO), which play roles in the relay of innate immune responses to infection and stress, or non-peptide hormones including ecdysone, which confers competence in the embryonic tracheal Drosocin response to bacterial infection and enhances humoral immunity under conditions of dehydration. Lastly, there could be requirement for additional processing to make bacterial ligands accessible for receptors in other tissues, as has been reported for Psidin, a lysosomal protein required in blood cells for degradation of engulfed bacteria and expression of Defensin in the fat body, although this mechanism may not be universal in all systems (Sanchez Bosch, 2019).

This work reveals an active role of endogenous Drosocin expression in survival after bacterial infection. Since the cloning of Drosocin and its classification as inducible antibacterial peptide, Drosocin has been studied for its transcriptional regulation, illustrating its induction under a variety of bacterial and other immune challenges. Drosocin structure and antimicrobial function have been studied in vitro and by overexpression from transgenes in Drosophila and in heterologous vertebrate systems. Consistent with the current findings, a recent study on CRISPR-based Drosocin null mutants reached similar conclusions regarding the requirement of endogenous Drosocin expression for animal survival following E. cloacae infection (Hanson, 2019). Expanding from these findings, this study reveals the anatomical features of Drosocin expression and its unique path of induction. In addition to Drosocin's role in animal survival after bacterial infection, the data suggest contribution of Drosocin to animal survival after injury through PBS injection. Injury has emerged as a factor that affects survival, a phenomenon for which the molecular mechanisms still remain to be determined. Alternatively, considering that the fly surface and living conditions are not sterile and survival experiments are performed over extended periods of time, it cannot be ruled out that PBS injections may have led to inadvertent infection with some low level contaminating microbes. A role for endogenous Drosocin levels in the antimicrobial response is strongly supported by independent data in the literature. Specifically, the minimum inhibitory concentration (MIC) of Drosocin against E. coli and E. cloacae was determined to be well within the range or below the endogenous concentration of Drosocin in the Drosophila hemolymph (MIC is 1 or 2 μM for the glycosylated forms, and 8 or 10 μM for the unglycosylated form, respectively, compared to 40 μM Drosocin in the Drosophila hemolymph (Sanchez Bosch, 2019).

In conclusion, this study revokes the use of adult Drosophila as effective model to study hematopoiesis, and establishes it as promising system for organismal immunity centering on the immune signaling relay at the reservoir of blood cells. At the evolutionary level, this model shows parallels with vertebrate immune cells of the lung and innate immune responses to bacterial infection. The Drosophila model opens countless avenues for exciting future research, e.g., to investigate additional molecular and cellular mechanisms in the immune signaling relay, the role and regulation of the system in the defense against pathogens that invade the trachea as natural route of infection, the use of the same axis by gram-positive or non-bacterial pathogens, and the induction of other AMPs and immune effector genes in the same axis of regulation (Sanchez Bosch, 2019).

Antimicrobial peptides extend lifespan in Drosophila

Antimicrobial peptides (AMPs) are important defense molecules of the innate immune system. High levels of AMPs are induced in response to infections to fight pathogens, whereas moderate levels induced by metabolic stress are thought to shape commensal microbial communities at barrier tissues. Single AMPs were expressed in adult flies either ubiquitously or in the gut by using the inducible GeneSwitch system to tightly regulate AMP expression. Activation of single AMPs, including Drosocin, were found to result in a significant extension of Drosophila lifespan. These animals showed reduced activity of immune pathways over lifetime, less intestinal regenerative processes, reduced stress response and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin induction protected the animals against infections with the natural Drosophila pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented the lifespan extending effect of Drosocin. This study provides new insights into the crosstalk of innate immunity, intestinal homeostasis and ageing (Loch, 2017).

The data demonstrate that both the ubiquitous as well as the gut specific induction of Dro and CecA1 is sufficient to significantly prolong lifespan of adult flies. These animals show reduced activation of classical immune pathways such as IMD and JAK-STAT over lifetime, less JNK and EGF pathway activity, required for regeneration, stem cell maintenance and a reduced stress response. These pathways usually increase their activity during ageing or upon bacterial challenge and are considered as markers for intestinal homeostasis. Evidence is provided for an improved intestinal barrier integrity which delays intestinal and organismal ageing and finally leads to longer lifespan of flies overexpressing Dro. It is suggested that the reduction of bacterial challenges upon Dro expression is responsible for these effects. Consistently, Dro expression was able to combat the infection with the natural Drosophila pathogen Pe in an oral infection model. Such a protection by single or several AMPs has been reported for some systemic infection models and also for the local protection against Pe by expressing Diptericin or Attacin. Antibiotics diminish the bacterial load of the food and the amount of the commensal as well as the pathogenic bacteria of the fly. It has been reported that neither the treatment with antibiotics nor the subsequent reduction or loss of commensal bacteria do seem to have an effect on the lifetime of male Drosophila flies. In contrast, in the experimental conditions using mated female flies, feeding antibiotics significantly prolonged lifespan. This may be explained by a different composition of commensal and pathogenic bacteria contained in the fly strains maintained under laboratory conditions or the differing gut physiology between male and female flies. Expression of Dro in flies treated with antibiotics did not further prolong the lifespan of these animals. It is assumed that this is due to the loss of bacterial targets, which Dro could act on. It has been reported that an overexpression of multiple as well as single AMPs by constitutive induction or by loss of their negative regulator caudal can lead to negative effects on gut health and survival. The effect of Dro expression has not been investigated in any study. One study observed a pathogenic phenotype of AMP expression only under conventional rearing conditions. This phenotype could be rescued by germ free conditions, explaining the observed effects with intestinal dysbiosis and a subsequent rupture of gut homeostasis. Although the study reports a negative effect of AMP induction in the gut, this still supports the hypothesis that AMPs are reliant on bacteria as targets to influence gut homeostasis and organismal lifespan. A shift in the commensal community structure favoring the growth of the usually minor species Gluconobacter morbifer G707 has been identified to be responsible for the pathogenic phenotype of altered AMP expression. In the current study, no a similar severe effect on the quality or the quantity of the microbiota was observed, nor could Gluconobacter be detected. Taken together, these results do not indicate that an effect of Dro on the commensal microbiota is responsible for the longevity of the flies, which nevertheless cannot be entirely exclude. On the other hand, several potentially pathogenic bacteria were identified in these flies, leading to the assumption that constitutive induction of AMP expression may effectively counteract the first steps of natural pathogen infections, thereby reducing the gastrointestinal infection rates over lifetime. Besides their antimicrobial function, other positive effects of AMPs on lifespan cannot be excluded. As an example, in one study Diptericin has been shown to prolong lifespan by increasing tolerance to oxidant stress. In vertebrates AMPs have been reported to inhibit tumor cell proliferation by targeting the negatively charged cancer cells (Loch, 2017).

AMPs could play an important role to mediate longevity in diverse contexts. As just one example, previous studies in Drosophila larvae have shown that AMPs can be activated infection-independent in response to the metabolic status by dFOXO, a transcriptional regulator of the insulin signaling pathway. Down regulation of insulin signaling leads to dFOXO activation and is associated with longevity in various animal systems. Loss and gain-of-function studies in adult flies indicate that Dro can be activated by dFOXO in the midgut improving the immune response. This hypothesis is also supported by a recent study showing that dFOXO signaling leads to AMP induction and is required to survive oral infections. Taken together these findings provide new insights into the network of metabolism, innate immunity, homeostasis and ageing, helping to understand the complex relationship of these fields of research (Loch, 2017).

Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide
Males with null mutation of Sex Peptide (SP) gene were compared to wild-type males for the ability to cause physiological changes in females that could be reversed by mifepristone. Males from wild-type strains decrease median female lifespan by average -51%. Feeding mifepristone increases life span of these females by average +106%. In contrast, SP-null males do not decrease female life span, and mifepristone increases median life span of these females by average +14%, which is equivalent to the effect of mifepristone in virgin females (average +16%). Expression of innate immune response transgenic reporter (Drosocin-GFP) is increased in females mated to wild-type males, and this expression is reduced by mifepristone. In contrast, SP-null males do not increase Drosocin-GFP reporter expression in the female. Similarly, mating increases endogenous microbial load, and this effect is reduced or absent in females fed mifepristone and in females mated to SP-null males; no loss of intestinal barrier integrity is detected using dye-leakage assay. Reduction of microbial load by treating adult flies with doxycycline reduces the effects of both mating and mifepristone on lifespan. Finally, mifepristone blocks the negative effect on life span caused by transgenic expression of SP in virgin females. The data support the conclusion that the majority of the life span-shortening, immune-suppressive and pro-inflammatory effects of mating are due to male SP, and demonstrate that mifepristone acts in females to counteract these effects of male SP (Tower, 2017).

Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption
Individuals frequently find themselves confronted with a variety of challenges that threaten their wellbeing. While some individuals face these challenges efficiently and thrive (resilient) others are unable to cope and may suffer persistent consequences (vulnerable). Resilience/vulnerability to sleep disruption may contribute to the vulnerability of individuals exposed to challenging conditions. With that in mind this study exploited individual differences in a fly's ability to form short-term memory (STM) following 3 different types of sleep disruption to identify the underlying genes. The analysis showed that in each category of flies examined, there are individuals that form STM in the face of sleep loss (resilient) while other individuals show dramatic declines in cognitive behavior (vulnerable). Molecular genetic studies revealed that Antimicrobial Peptides, factors important for innate immunity, were candidates for conferring resilience/vulnerability to sleep deprivation. Specifically, Metchnikowin (Mtk), drosocin (dro) and Attacin (Att) transcript levels seemed to be differentially increased by sleep deprivation in glia (Mtk), neurons (dro) or primarily in the head fat body (Att). Follow-up genetic studies confirmed that expressing Mtk in glia but not neurons, and expressing dro in neurons but not glia, disrupted memory while modulating sleep in opposite directions. These data indicate that various factors within glia or neurons can contribute to individual differences in resilience/vulnerability to sleep deprivation (Dissel, 2015). .

Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster

In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. This study provides evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. Early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. It was also shown that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down-regulated and activation and translocation of transcription factor Relish is also affected (Verma, 2015).

The Dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults

There are a number of different controls on the expression of the antifungal polypeptide gene drosomycin in adults: the receptor Toll, intracellular components of the dorsoventral signaling pathway (Tube, Pelle, and Cactus), and the extracellular Toll ligand, Spätzle, but not the NF-kappaB related transcription factor Dorsal. Mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. In Tl-deficient adults, the cecropin A and, to a lesser extent, attacin, drosomycin and defensin genes are only minimally inducible, in contrast with the diptericin and drosocin genes, which remain fully inducible in this context. The drosomycin gene induction is not affected in mutants deficient in gastrulation defective, snake and easter, all upstream of spätzle in the dorsoventral pathway. The involvement of Spätzle in the drosomycin induction pathway is unexpected, since, in contrast with cat, pll, tub, and Tl, the spz mutant shows no striking zygotic phenotype. The partner of Cact in the drosomycin induction pathway has not yet been identified, but it is probably a member of the Rel family, possibly Dorsal-related immunity factor (Lemaitre, 1996).


Search PubMed for articles about Drosophila Drosocin

Dissel, S., Seugnet, L., Thimgan, M. S., Silverman, N., Angadi, V., Thacher, P. V., Burnham, M. M. and Shaw, P. J. (2015). Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption. Brain Behav Immun 47: 75-85. PubMed ID: 25451614

Gold, K. S. and Bruckner, K. (2014). Drosophila as a model for the two myeloid blood cell systems in vertebrates. Exp Hematol 42(8): 717-727. PubMed ID: 24946019

Gold, K. S. and Bruckner, K. (2015). Macrophages and cellular immunity in Drosophila melanogaster. Semin Immunol 27(6): 357-368. PubMed ID: 27117654

Hanson, M. A., Dostalova, A., Ceroni, C., Poidevin, M., Kondo, S. and Lemaitre, B. (2019). Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach. Elife 8. PubMed ID: 30803481

Lemaitre, B., et al. (1996). The Dorsoventral regulatory gene cassette saätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973-983. PubMed Citation: 8808632

Loch, G., Zinke, I., Mori, T., Carrera, P., Schroer, J., Takeyama, H. and Hoch, M. (2017). Antimicrobial peptides extend lifespan in Drosophila. PLoS One 12(5): e0176689. PubMed ID: 28520752

Makhijani, K., Alexander, B., Tanaka, T., Rulifson, E. and Bruckner, K. (2011). The peripheral nervous system supports blood cell homing and survival in the Drosophila larva. Development 138(24): 5379-5391. PubMed ID: 22071105

Makhijani, K. and Bruckner, K. (2012). Of blood cells and the nervous system: hematopoiesis in the Drosophila larva. Fly (Austin) 6(4): 254-260. PubMed ID: 23022764

Sanchez Bosch, P., Makhijani, K., Herboso, L., Gold, K. S., Baginsky, R., Woodcock, K. J., Alexander, B., Kukar, K., Corcoran, S., Jacobs, T., Ouyang, D., Wong, C., Ramond, E. J. V., Rhiner, C., Moreno, E., Lemaitre, B., Geissmann, F. and Bruckner, K. (2019). Adult Drosophila lack hematopoiesis but rely on a blood cell reservoir at the respiratory epithelia to relay infection signals to surrounding tissues. Dev Cell. 51(6):787-803 PubMed ID: 31735669

Tower, J., Landis, G.N., Shen, J., Choi, R., Fan, Y., Lee, D. and Song, J. (2017). Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide. Biogerontology [Epub ahead of print]. PubMed ID: 28451923

Verma, P. and Tapadia, M. G. (2015). Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster. Mol Immunol 66: 325-339. PubMed ID: 25931442

Biological Overview

date revised: 15 May 2022

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