Characterising four Sarconesiopsis magellanica (Diptera: Calliphoridae) larval fat body-derived antimicrobial peptides

The mosquito Aedes aegypti is the most notorious vector of illness-causing viruses. The use of entomopathogenic fungi as bioinsecticides is a promising alternative for the development of novel mosquito control strategies. We investigate whether differences in immune responses could be responsible for modifications in survival rates of insects following different feeding regimes. Sucrose and blood-fed adult A. aegypti females were sprayed with M. anisopliae 1 × 106 conidia mL−1, and after 48 h, the midgut and fat body were dissected. We used RT-qPCR to monitor the expression of Cactus and REL1 (Toll pathway), IMD, REL2, and Caspar (IMD pathway), STAT and PIAS (JAK-STAT pathway), as well as the expression of antimicrobial peptides (Defensin A, Attacin and Cecropin G). REL1 and REL2 expression in both the midgut and fat body were higher in blood-fed fungus-challenged A. aegypti than in sucrose-fed counterparts. Interestingly, infection of sucrose-fed insects induced Cactus expression in the fat body, a negative regulator of the Toll pathway. The IMD gene was upregulated in the fat body in response to fungal infection after a blood meal. Additionally, we observed the induction of antimicrobial peptides in the blood-fed fungus-challenged insects. This study suggests that blood-fed A. aegypti are less susceptible to fungal infection due to the rapid induction of Toll and IMD immune pathways.

Download Full-text

Prostaglandin E2 modulates the expression of antimicrobial peptides in the fat body and midgut ofAnopheles albimanus

Archives of Insect Biochemistry and Physiology ◽

10.1002/arch.20232 ◽

2008 ◽

Vol 68 (1) ◽

pp. 14-25 ◽

Cited By ~ 22

Author(s):

F.L. García Gil de Muñoz ◽

J. Martínez-Barnetche ◽

H. Lanz-Mendoza ◽

M.H. Rodríguez ◽

F.C. Hernández-Hernández

Keyword(s):

Antimicrobial Peptides ◽

Prostaglandin E2 ◽

Fat Body

Download Full-text

Two Roles for the Tenebrio molitor Relish in the Regulation of Antimicrobial Peptides and Autophagy-Related Genes in Response to Listeria monocytogenes

Insects ◽

10.3390/insects11030188 ◽

2020 ◽

Vol 11 (3) ◽

pp. 188 ◽

Cited By ~ 5

Author(s):

Maryam Keshavarz ◽

Yong Hun Jo ◽

Tariku Tesfaye Edosa ◽

Yeon Soo Han

Keyword(s):

Listeria Monocytogenes ◽

Antimicrobial Peptides ◽

Fat Body ◽

Early Stage ◽

Tenebrio Molitor ◽

Imd Pathway ◽

Atg Genes ◽

Notable Increase ◽

Significant Mortality

Relish is a key NF-κB transcription factor of the immune-deficiency (Imd) pathway that combats infection by regulating antimicrobial peptides (AMPs). Understanding of the fundamental role of Tenebrio molitor Relish (TmRelish) in controlling of Listeria monocytogenes virulence through the regulation of both AMPs and autophagy-related (ATG) genes is unclear. Here, we show that TmRelish transcripts were highly abundant in the larval fat body and hemocytes compared to the gut upon L. monocytogenes infection. Furthermore, significant mortality was observed in TmRelish-silenced larvae after intracellular insult. To investigate the cause of this lethality, we measured the induction of AMPs and ATG genes in the TmRelish dsRNA-treated T. molitor larvae. The expression of TmTenecin-1, TmTenecin-4, TmColeptericin-1, TmAttacin-2, and TmCecropin-2 were suppressed in the fat body and hemocytes of dsTmRelish-injected larvae during L. monocytogenes infection. In addition, TmRelish knockdown led to a noticeable downregulation of TmATG1 (a serine-threonine protein kinase) in the fat body and hemocytes of young larvae 6 h post-infection (pi). The notable increase of autophagy genes in the early stage of infection (6 h pi), suggesting autophagy response is crucial for Listeria clearance. Taken together, these results suggest that TmRelish plays pivotal roles in not only regulation of AMP genes but also induction of autophagy genes in response to L. monocytogenes challenge in fat body and hemocytes of T. molitor larvae. Furthermore, negative regulation of several AMPs by TmRelish in the fat body, hemocytes, and gut leaves open the possibility of a crosstalk between Toll and Imd pathway.

Download Full-text

Antimicrobial peptides modulate long-term memory

10.1101/328286 ◽

2018 ◽

Cited By ~ 1

Author(s):

Raquel Barajas Azpeleta ◽

Jianping Wu ◽

Jason Gill ◽

Ryan Welte ◽

Chris Seidel ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Defense Mechanism ◽

Short Term Memory ◽

Fat Body ◽

Long Term Memory ◽

Short Term ◽

Term Memory ◽

Host Defense Mechanism ◽

Instinctive Behavior

AbstractAntimicrobial peptides act as a host defense mechanism and regulate the commensal microbiome. To obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Surprisingly, we find that two immune peptides with antimicrobial activity, Diptericin B and Gram-Negative Bacteria Binding Protein like 3, regulate long-term but not short-term memory or instinctive behavior in Drosophila. The cellular requirement of these two peptides is distinct: head fat body for DptB, and neurons for GNBP-like3. That antimicrobial peptides influence memory provides a novel example of the emerging link between the immune and nervous systems and reveals that some immune peptides may have been repurposed in the nervous system.

Download Full-text

Innate immune signaling in Drosophila shifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis in an ER stress-dependent manner

10.1101/2020.03.01.972208 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brittany A. Martínez ◽

Scott Yeudall ◽

Rosalie G. Hoyle ◽

J. David Castle ◽

Norbert Leitinger ◽

...

Keyword(s):

Immune Response ◽

Endoplasmic Reticulum ◽

Lipid Metabolism ◽

Antimicrobial Peptides ◽

Fat Body ◽

Lipid Storage ◽

Phospholipid Synthesis ◽

Fat Storage ◽

Toll Signaling ◽

Kennedy Pathway

AbstractDuring infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize and kill invading pathogens. In Drosophila, these effectors are antimicrobial peptides (AMPs) that are produced in the fat body, an organ that also serves as a major lipid storage depot. Here we asked how activation of Toll signaling in the larval fat body perturbs lipid homeostasis to understand how cells meet the metabolic demands of the immune response. We find that genetic activation of fat body Toll signaling leads to a tissue-autonomous reduction in triglyceride storage that is paralleled by decreased transcript levels of Lipin, which synthesizes diacylglycerol, and midway, which carries out the final step of triglyceride synthesis. In contrast, we discovered that Kennedy pathway enzymes, such as easily shocked and Pcyt1, that synthesize membrane phospholipids are induced by the Toll pathway. Mass spectrometry analysis revealed elevated levels of major phosphatidylcholine and phosphatidylethanolamine species in fat bodies with active Toll signaling. The induction of Kennedy pathway enzymes in response to Toll signaling required the unfolded response mediator Xbp1 but was blunted by deleting AMP genes and thereby reducing secretory demand elicited by Toll activation. Consistent with these findings, endoplasmic reticulum volume is expanded in fat body cells with active Toll signaling, as determined by transmission electron microscopy. Our results establish that Toll signaling induces a shift in anabolic lipid metabolism, accompanied by changes in key lipid synthesis enzymes, that may serve the immediate demand for AMP synthesis and secretion but that ultimately leads to the long-term consequence of insufficient nutrient storage.Author summaryFighting infection requires that immune cells synthesize antimicrobial peptides and antibodies and carry out cellular processes like phagocytosis to destroy microbes and clear infected cells. During infection, metabolic processes support and direct immune function. Here, we use the fruit fly Drosophila melanogaster as a model system to understand the interaction between immunity and metabolism. In Drosophila larvae, infection leads to tremendous production of antimicrobial peptides that destroy invading microbes. These peptides are made in the fat body, an organ that is also the site of fat storage. Activating the immune response reduces lipid storage but increases the production of phospholipids that form the membranes of organelles such as the endoplasmic reticulum. This organelle is the starting point for synthesis and secretion of antimicrobial peptides, and its volume is increased in response to immune activation. Shifting metabolism from fat storage to membrane phospholipid synthesis supports the immune response. However, this comes at the expense of the ability to withstand other types of stress such as food scarcity. These findings are important because they suggest that some of the metabolic changes induced by fighting infection may become pathological if they are maintained over long periods of time.

Download Full-text

Functional analysis of a NF-κB transcription factor in the immune defense of Oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae)

Bulletin of Entomological Research ◽

10.1017/s0007485316000845 ◽

2016 ◽

Vol 107 (2) ◽

pp. 251-260 ◽

Cited By ~ 5

Author(s):

Z. Shi ◽

H. Liang ◽

Y. Hou

Keyword(s):

Transcription Factor ◽

Antimicrobial Peptides ◽

Fat Body ◽

Quantitative Polymerase Chain Reaction ◽

Fruit Fly ◽

Polymerase Chain Reaction Analysis ◽

Immune Defense ◽

Bactrocera Dorsalis ◽

Transcription Activator ◽

Reading Frame

AbstractAlthough some novel antimicrobial peptides (AMP) have been successfully isolated from Bactrocera dorsalis Hendel, the mechanisms underlying the induction of these peptides are still elusive. The homolog of NF-κB transcription factor Relish, designated as BdRelish, was cloned from B. dorsalis. The full length cDNA of BdRelish is 3954 bp with an open reading frame that encodes 1013 amino acids. Similar to Drosophila Relish and the mammalian p100, it is a compound protein containing a conserved Rel homology domain, an IPT (Ig-like, plexins, transcription factors) domain and an IκB-like domain (four ankyrin repeats), the nuclear localization signal RKRRR is also detected at the residues 449–453, suggesting that it has homology to Relish and it is a member of the Rel family of transcription activator proteins. Reverse transcription quantitative polymerase chain reaction analysis reveals that BdRelish mRNAs are detected in different quantities from various tissues and the highest transcription level of BdRelish is determined in fat body. The injection challenge of Escherichia coli and Staphylococcus aureas significantly upregulated the expression of BdRelish. The injection of BdRelish dsRNA markedly reduced the expression of BdRelish and decreased the transcription magnitude of antimicrobial peptides. Individuals injected BdRelish dsRNA died at a significantly faster rate compared with the control groups. Therefore, BdRelish is vital for the transcription of AMPs to attack the invading bacteria.

Download Full-text

Characterization of a Defensin from the Sand Fly Phlebotomus duboscqi Induced by Challenge with Bacteria or the Protozoan Parasite Leishmania major

Infection and Immunity ◽

10.1128/iai.72.12.7140-7146.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7140-7146 ◽

Cited By ~ 85

Author(s):

Nathalie Boulanger ◽

Carl Lowenberger ◽

Petr Volf ◽

Raul Ursic ◽

Lucie Sigutova ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Leishmania Major ◽

Fat Body ◽

Protozoan Parasite ◽

Sand Fly ◽

Parasitic Infections ◽

Knockout Mutants ◽

Insect Defensin ◽

Phlebotomus Duboscqi ◽

Gut Pathogens

ABSTRACT Antimicrobial peptides are major components of the innate immune response of epithelial cells. In insect vectors, these peptides may play a role in the control of gut pathogens. We have analyzed antimicrobial peptides produced by the sand fly Phlebotomus duboscqi, after challenge by injected bacteria or feeding with bacteria or the protozoan parasite Leishmania major. A new hemolymph peptide with antimicrobial activity was identified and shown to be a member of the insect defensin family. Interestingly, this defensin exhibits an antiparasitic activity against the promastigote forms of L. major, which reside normally within the sand fly midgut. P. duboscqi defensin could be induced by both hemolymph or gut infections. Defensin mRNA was induced following infection by wild-type L. major, and this induction was much less following infections with L. major knockout mutants that survive poorly in sand flies, due to specific deficiencies in abundant cell surface glycoconjugates containing phosphoglycans (including lipophosphoglycan). The ability of gut pathogens to induce gut as well as fat body expression of defensin raises the possibility that this antimicrobial peptide might play a key role in the development of parasitic infections.

Download Full-text

Antimicrobial peptides from Bombyx mori: a splendid immune defense response in silkworms

RSC Advances ◽

10.1039/c9ra06864c ◽

2020 ◽

Vol 10 (1) ◽

pp. 512-523 ◽

Cited By ~ 3

Author(s):

Jannatun Nesa ◽

Abdul Sadat ◽

Danieli F. Buccini ◽

Ahmet Kati ◽

Amit K. Mandal ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Bombyx Mori ◽

Defense Response ◽

Fat Body ◽

Immune Defense ◽

Microbial Challenge

AMPs produced by B. mori induced by microbial challenge in the fat body.

Download Full-text

TmDorX2 positively regulates antimicrobial peptides in Tenebrio molitor gut, fat body, and hemocytes in response to bacterial and fungal infection

Scientific Reports ◽

10.1038/s41598-019-53497-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 11

Author(s):

Maryam Keshavarz ◽

Yong Hun Jo ◽

Ki Beom Park ◽

Hye Jin Ko ◽

Tariku Tesfaye Edosa ◽

...

Keyword(s):

Transcription Factors ◽

Antimicrobial Peptides ◽

Post Infection ◽

Fat Body ◽

Tenebrio Molitor ◽

Malpighian Tubules ◽

Whole Body ◽

Mrna Levels ◽

E Coli ◽

Pathogen Invasion

AbstractDorsal, a member of the nuclear factor-kappa B (NF-κB) family of transcription factors, is a critical downstream component of the Toll pathway that regulates the expression of antimicrobial peptides (AMPs) against pathogen invasion. In this study, the full-length ORF of Dorsal was identified from the RNA-seq database of the mealworm beetle Tenebrio molitor (TmDorX2). The ORF of TmDorX2 was 1,482 bp in length, encoding a polypeptide of 493 amino acid residues. TmDorX2 contains a conserved Rel homology domain (RHD) and an immunoglobulin-like, plexins, and transcription factors (IPT) domain. TmDorX2 mRNA was detected in all developmental stages, with the highest levels observed in 3-day-old adults. TmDorX2 transcripts were highly expressed in the adult Malpighian tubules (MT) and the larval fat body and MT tissues. After challenging the larvae with Staphylococcus aureus and Escherichia coli, the TmDorX2 mRNA levels were upregulated 6 and 9 h post infection in the whole body, fat body, and hemocytes. Upon Candida albicans challenge, the TmDorX2 mRNA expression were found highest at 9 h post-infection in the fat body. In addition, TmDorX2-knockdown larvae exposed to E. coli, S. aureus, or C. albicans challenge showed a significantly increased mortality rate. Furthermore, the expression of 11 AMP genes was downregulated in the gut and fat body of dsTmDorX2-injected larvae upon E. coli challenge. After C. albicans and S. aureus challenge of dsTmDorX2-injected larvae, the expression of 11 and 10 AMPs was downregulated in the gut and fat body, respectively. Intriguingly, the expression of antifungal transcripts TmTenecin-3 and TmThaumatin-like protein-1 and -2 was greatly decreased in TmDorX2-silenced larvae in response to C. albicans challenge, suggesting that TmDorX2 regulates antifungal AMPs in the gut in response to C. albicans infection. The AMP expression profiles in the fat body, hemocytes, gut, and MTs suggest that TmDorX2 might have an important role in promoting the survival of T. molitor larvae against all mentioned pathogens.

Download Full-text

Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors in Drosophila mxc mutants

10.1101/452961 ◽

2018 ◽

Cited By ~ 4

Author(s):

Mayo Araki ◽

Rie Awane ◽

Tetsuya Sato ◽

Yasuyuki Ohkawa ◽

Yoshihiro H. Inoue

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Tumor Cells ◽

Innate Immune System ◽

Fat Body ◽

Human Cancer ◽

Ectopic Expression ◽

Innate Immune ◽

Hematopoietic Tissue ◽

Hematopoietic Organ

AbstractThe innate immune response is the first line of defense against microbial infections. In Drosophila, three immune pathways induce the synthesis of antimicrobial peptides (AMPs) in the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells. However, little is known about their anti-tumor effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval hematopoietic organ called the lymph gland (LG). Here, using RNA-Seq analysis, we found that many immunoresponsive genes, including AMP genes, were up-regulated in the mutants. Down-regulation of these pathways by either a Toll or an imd mutation enhanced the tumor phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress progression of hematopoietic tumors by inducing AMP gene expression. Overexpression of any one of these five AMPs resulted in enhanced apoptosis in the mutant LGs, while no apoptosis signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating hemocyte-like cells, which were associated with LG regions showing reduced cell-to-cell adhesion in the mutants; another AMP, diptericin, was directly localized on the tumors without intermediating hemocytes. These results lead us to conclude that the AMPs have a specific cytotoxic effect that enhance apoptosis exclusively in the tumor cells.Summary statement:Antimicrobial peptides can be associated with tumor cells generated in a hematopoietic tissue in Drosophila mxc mutants and have an anti-tumor effect in suppressing their growth.

Download Full-text