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Insects are established models for understanding host-pathogen interactions and innate immune mechanisms. The innate immune system in insects is highly efficient in recognizing and opposing pathogens that cause detrimental effects during infection. The cuticular layer which covers the superficial layer of the insect body participates in host defense and wound healing by inducing innate immune responses. Previous studies have started to address the involvement of cuticular genes in conferring resistance to insect pathogens, particularly those that infect by disrupting the insect cuticle. For example, the cuticular gene Transglutaminase (TG) in Drosophila melanogaster plays a structural role in cuticle formation and blood coagulation and also possesses immune properties against pathogenic infection. However, more information is becoming available about the immune function of other cuticular gene families in insects. In this review, we aim to highlight the recent advances in insect cuticular immunity and address the necessity of pursuing further research to fill the existing gaps in this important field of insect immunology. This information will lead to novel strategies for the efficient management of agricultural insect pests and vectors of plant and human disease.
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Imunidade Inata , Insetos , Animais , Insetos/imunologia , Insetos/genética , Imunidade Inata/genética , Interações Hospedeiro-Patógeno/imunologia , Interações Hospedeiro-Patógeno/genética , Proteínas de Insetos/genética , Proteínas de Insetos/imunologia , Proteínas de Insetos/metabolismo , Drosophila melanogaster/imunologia , Drosophila melanogaster/genética , Drosophila melanogaster/microbiologiaRESUMO
Despite impressive advances in the broad field of innate immunity, our understanding of the molecules and signaling pathways that control the host immune response to nematode infection remains incomplete. We have shown recently that Transforming Growth Factor-ß (TGF-ß) signaling in the fruit fly Drosophila melanogaster is activated by nematode infection and certain TGF-ß superfamily members regulate the D. melanogaster anti-nematode immune response. Here, we investigate the effect of an entomopathogenic nematode infection factor on host TGF-ß pathway regulation and immune function. We find that Heterorhabditis bacteriophora serine carboxypeptidase activates the Activin branch in D. melanogaster adults and the immune deficiency pathway in Activin-deficient flies, it affects hemocyte numbers and survival in flies deficient for Activin signaling, and causes increased intestinal steatosis in Activin-deficient flies. Thus, insights into the D. melanogaster signaling pathways and metabolic processes interacting with H. bacteriophora pathogenicity factors will be applicable to entomopathogenic nematode infection of important agricultural insect pests and vectors of disease.
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Proteínas de Drosophila , Drosophila melanogaster , Metabolismo dos Lipídeos , Transdução de Sinais , Animais , Drosophila melanogaster/parasitologia , Drosophila melanogaster/imunologia , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Carboxipeptidases/metabolismo , Carboxipeptidases/genética , Ativinas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Rabditídios/fisiologia , Imunidade Inata , Proteínas de TransporteRESUMO
Drosophila melanogaster has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity and virus-induced pathology. Previous studies have shown that the presence of Wolbachia endosymbionts in D. melanogaster confers resistance to infection by certain viral pathogens. Zika virus is an important vector-borne pathogen that has recently expanded its range due to the wide geographical distribution of the mosquito vector. Here, we describe the effect of Wolbachia on the immune response of D. melanogaster adult flies following Zika virus infection. First, we show that the presence of Wolbachia endosymbionts promotes the longevity of uninfected D. melanogaster wild type adults and increases the survival response of flies following Zika virus injection. We find that the latter effect is more pronounced in females rather than in males. Then, we show that the presence of Wolbachia regulates Zika virus replication during Zika virus infection of female flies. In addition, we demonstrate that the antimicrobial peptide-encoding gene Drosocin and the sole Jun N-terminal kinase-specific MAPK phosphatase Puckered are upregulated in female adult flies, whereas the immune and stress response gene TotM is upregulated in male individuals. Finally, we find that the activity of RNA interference and Toll signaling remain unaffected in Zika virus-infected female and male adults containing Wolbachia compared to flies lacking the endosymbionts. Our results reveal that Wolbachia endosymbionts in D. melanogaster affect innate immune signaling activity in a sex-specific manner, which in turn influences host resistance to Zika virus infection. This information contributes to a better understanding of the complex interrelationship between insects, their endosymbiotic bacteria, and viral infection. Interpreting these processes will help us design more effective approaches for controlling insect vectors of infectious disease.
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Insects are one of the most successful animals in nature, and entomopathogenic fungi play a significant role in the natural epizootic control of insect populations in many ecosystems. The interaction between insects and entomopathogenic fungi has continuously coevolved over hundreds of millions of years. Many components of the insect innate immune responses against fungal infection are conserved across phyla. Additionally, behavioral responses, which include avoidance, grooming, and/or modulation of body temperature, have been recognized as important mechanisms for opposing fungal pathogens. In an effort to investigate possible cross-talk and mediating mechanisms between these fundamental biological processes, recent studies have integrated and/or explored immune and behavioral responses. Current information indicates that during discrete stages of fungal infection, several insect behavioral and immune responses are altered simultaneously, suggesting important connections between the two systems. This review synthesizes recent advances in our understanding of the physiological and molecular aspects influencing cross-talk between behavioral and innate immune antifungal reactions, including chemical perception and olfactory pathways.
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Ecossistema , Micoses , Animais , Insetos/microbiologia , Imunidade Inata , FungosRESUMO
TGF-ß signaling pathways are present in diverse animal species, which indicates their evolutionary importance in modulating several conserved biological processes and maintaining host homeostasis by adjusting the activity of innate immune mechanisms. Drosophila melanogaster utilizes two related but separable cascades of the canonical TGF-ß signaling pathway: The Bone Morphogenetic Protein and Activin branches. Recent studies have produced significant information on the immune role of TGF-ß signaling in the fruit fly model during response against certain bacterial pathogens. Results from further investigations have generated novel insights into the role of Drosophila TGF-ß signaling molecules as immune regulators opposing infection against nematode parasites and their mutualistic bacterial partners. This knowledge has revealed a previously unknown layer of the host innate immune system. Here we summarize these recent breakthroughs focusing on the participation of TGF-ß signaling factors in various Drosophila immune processes in relation to infection with potent bacteria and nematode parasites. The presented information provides important clues indicating directions for future research into the design of novel strategies for the effective control of infectious diseases caused by bacterial pathogens and parasitic nematodes.
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Drosophila melanogaster is an excellent model for dissecting innate immune signaling and functions. Humoral and cellular immune mechanisms in the fly take place in the hemolymph, where host defense components are secreted and act in response to microbial invaders. Studying hemolymph factors is critical for understanding the regulation of the host's antimicrobial immune system. Therefore, methods for extracting the fly hemolymph efficiently and in sufficient quantities are essential for isolating and characterizing immune proteins and peptides. Here, we describe a novel and simple hemolymph isolation protocol for single D. melanogaster male and female adults. This procedure substantially improves the already used technique and allows fly immunologists to explore innate immune hemolymph activity in D. melanogaster individuals.
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Drosophila melanogaster relies on an evolutionarily conserved innate immune system to protect itself from a wide range of pathogens, making it a convenient genetic model to study various human pathogenic viruses and host antiviral immunity. Here we explore for the first time the contribution of the Drosophila phenoloxidase (PO) system to host survival and defenses against Zika virus (ZIKV) infection by analyzing the role of mutations in the three prophenoloxidase (PPO) genes in female and male flies. We show that only PPO1 and PPO2 genes contribute to host survival and appear to be upregulated following ZIKV infection in Drosophila. Also, we present data suggesting that a complex regulatory system exists between Drosophila PPOs, potentially allowing for a sex-dependent compensation of PPOs by one another or other immune responses such as the Toll, Imd, and JAK/STAT pathways. Furthermore, we show that PPO1 and PPO2 are essential for melanization in the hemolymph and the wound site in flies upon ZIKV infection. Our results reveal an important role played by the melanization pathway in response to ZIKV infection, hence highlighting the importance of this pathway in insect host defense against viral pathogens and potential vector control strategies to alleviate ZIKV outbreaks.
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Infecção por Zika virus , Zika virus , Animais , Masculino , Feminino , Humanos , Drosophila melanogaster/genética , Infecção por Zika virus/genética , Zika virus/metabolismo , Catecol Oxidase/genética , Catecol Oxidase/metabolismo , Imunidade InataRESUMO
Entomopathogenic nematodes are commonly used to control insect pest populations in the field. They also contribute substantially to understanding the molecular basis of nematode pathogenicity and insect anti-nematode immunity. Here, we tested the effect of the entomopathogenic nematode Steinernema hermaphroditum on the survival and immune signaling regulation of Drosophila melanogaster wild type larvae. Our results indicate that S. hermaphroditum infective juveniles are pathogenic toward D. melanogaster larvae, but they fail to activate certain immune pathway readout genes. These findings imply that S. hermaphroditum employs mechanisms that allow these parasitic nematodes to interfere with the D. melanogaster immune system.
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The fruit fly Drosophila melanogaster is an excellent model for dissecting the molecular and functional bases of bacterial pathogenicity and host antibacterial immune response. The Gram-negative bacterium Photorhabdus luminescens is an insect-specific pathogen that forms a mutualistic relationship with the entomopathogenic nematode Heterorhabditis bacteriophora . Here we find that oral infection of D. melanogaster larvae with P. luminescens moderately reduces their survival ability while the bacteria replicate efficiently in the infected insects. This information will contribute towards understanding host gut immunity against potent bacterial pathogens.
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Insect herbivores frequently encounter plant defense molecules, but the physiological and ecological consequences for their immune systems are not fully understood. The majority of studies attempting to relate levels of plant defensive chemistry to herbivore immune responses have used natural population or species-level variation in plant defensive chemistry. Yet, this potentially confounds the effects of plant defense chemistry with other potential plant trait differences that may affect the expression of herbivore immunity. We used an artificial diet containing known quantities of a plant toxin (4-methylsulfinylbutyl isothiocyanate; 4MSOB-ITC or ITC, a breakdown product of the glucosinolate glucoraphanin upon herbivory) to explicitly explore the effects of a plant toxin on the cellular and humoral immune responses of the generalist herbivore Trichoplusia ni (Lepidoptera: Noctuidae) that frequently feeds on glucosinolate-containing plants. Caterpillars feeding on diets with high concentrations of ITC experienced reduced survivorship and growth rates. High concentrations of ITC suppressed the appearance of several types of hemocytes and melanization activity, which are critical defenses against parasitic Hymenoptera and microbial pathogens. In terms of T. ni humoral immunity, only the antimicrobial peptide (AMP) genes lebocin and gallerimycin were significantly upregulated in caterpillars fed on diets containing high levels of ITC relative to caterpillars that were provided with ITC-free diet. Surprisingly, challenging caterpillars with a non-pathogenic strain of Escherichia coli resulted in the upregulation of the AMP gene cecropin. Feeding on high concentrations of plant toxins hindered caterpillar development, decreased cellular immunity, but conferred mixed effects on humoral immunity. Our findings provide novel insights into the effects of herbivore diet composition on insect performance demonstrating the role of specific plant defense toxins that shape herbivore immunity and trophic interactions.
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Alcaloides , Mariposas , Animais , Herbivoria , Larva/fisiologia , Glucosinolatos , Imunidade Humoral , Mariposas/fisiologia , Plantas , Alcaloides/farmacologia , Isotiocianatos/farmacologiaRESUMO
Significant progress has been made in recent years on exploring immunometabolism, a field that integrates two processes essential for maintaining tissue and organismal homeostasis, immunity and metabolism. The nematode parasite Heterorhabditis gerrardi, its mutualistic bacteria Photorhabdus asymbiotica, and the fruit fly Drosophila melanogaster constitute a unique system to investigate the molecular basis of host immunometabolic response to nematode-bacterial complexes. In this study, we explored the contribution of the two major immune signaling pathways, Toll and Imd, to sugar metabolism in D. melanogaster larvae during infection with H. gerrardi nematodes. We infected Toll or Imd signaling loss-of-function mutant larvae with H. gerrardi nematodes and assessed larval survival ability, feeding rate, and sugar metabolism. We found no significant differences in the survival ability or levels of sugar metabolites in any of the mutant larvae when responding to H. gerrardi infection. However, we found that the Imd mutant larvae have higher feeding rate than controls during the early stages of infection. In addition, feeding rates are lower in Imd mutants relative to the control larvae as the infection progresses. We further showed that Dilp2 and Dilp3 gene expression increases in Imd mutants compared to controls early in the infection, but their expression levels decrease at later times. These findings indicate that Imd signaling activity regulates the feeding rate and Dilp2 and Dilp3 expression in D. melanogaster larvae infected with H. gerrardi. Results from this study facilitate our understanding of the link between host innate immunity and sugar metabolism in the context of infectious diseases caused by parasitic nematodes.
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The gut epithelia of virtually all animals harbor complex microbial communities that play an important role in maintaining immune and cellular homeostasis. Gut microbiota have evolutionarily adapted to the host gut environment, serving as key regulators of intestinal stem cells to promote a healthy gut barrier and modulate epithelial self-renewal. Disruption of these populations has been associated with inflammatory disorders or cancerous lesions of the intestine. However, the molecular mechanisms controlling gut-microbe interactions are only partially understood due to the high diversity and biologically dynamic nature of these microorganisms. This article reviews the current knowledge on Drosophila gut microbiota and its role in signaling pathways that are crucial for the induction of distinct homeostatic and immune responses. Thanks to the genetic tractability of Drosophila and its cultivable and simple microbiota, this association model offers new efficient tools for investigating the crosstalk between a host and its microbiota while providing a framework for a better understanding of the ecological and evolutionary roles of the microbiome.
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Microbioma Gastrointestinal , Microbiota , Animais , Drosophila , Epitélio , HomeostaseRESUMO
Severe neurological complications affecting brain growth and function have been well documented in newborn and adult patients infected by Zika virus (ZIKV), but the underlying mechanisms remain unknown. Here we use a Drosophila melanogaster mutant, cheesehead (chs), with a mutation in the brain tumor (brat) locus that exhibits both aberrant continued proliferation and progressive neurodegeneration in the adult brain. We report that temperature variability is a key driver of ZIKV pathogenesis, thereby altering host mortality and causing motor dysfunction in a sex-dependent manner. Furthermore, we show that ZIKV is largely localized to the brat chs brain and activates the RNAi and apoptotic immune responses. Our findings establish an in vivo model to study host innate immune responses and highlight the need of evaluating neurodegenerative deficits as a potential comorbidity in ZIKV-infected adults.
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The entomopathogenic nematode (EPN) Heterorhabditis bacteriophora infects a wide range of insect hosts with the aid of its mutualistic bacteria Photorhabdus luminescens. While the mutualistic relationship between H. bacteriophora and P. luminescens and the infectivity of the nematode-bacteria complex have been characterized, how nematode fitness is affected by entomopathogenic bacteria existing in association with other EPN species remains poorly understood. In this study, the survival of H. bacteriophora infective juveniles containing or lacking P. luminescens was tested against the entomopathogenic bacteria Xenorhabdus nematophila and Photorhabdus asymbiotica as well as the non-pathogenic Escherichia coli. While X. nematophila and E. coli did not significantly affect the survival of H. bacteriophora, P. asymbiotica exerted a significant effect on nematode survival, particularly on those lacking P. luminescens. These results imply that P. asymbiotica encodes factors that are pathogenic to EPNs. Future efforts will focus on the identification of the bacterial molecular components that induce these effects. This study makes an important contribution to a growing body of research aimed at exploiting the full potential of nematode-bacterial complexes for eliminating noxious insect pests and treating infectious diseases caused by parasitic nematodes.
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Nematoides , Photorhabdus , Animais , Escherichia coli , SimbioseRESUMO
INTRODUCTION: Odorant-binding proteins (OBPs) are a class of small molecular weight soluble proteins that exist as expanded gene families in all insects, acting as ligand carriers mediating olfaction and other physiological processes. During fungal infection, a subset of insect OBPs were shown to be differentially expressed. OBJECTIVES: We tested whether the altered expression of insect OBPs during pathogenic infection plays a role in behavioral or immune interactions between insect hosts and their pathogens. METHODS: A wide range of techniques including RNAi-directed knockdown, heterologous protein expression, electrophysiological/behavioral analyses, transcriptomics, gut microbiome analyses, coupled with tandem mass spectrometry ion monitoring, were used to characterize the function of a locust OBP in host behavioral and immune responses. RESULTS: The entomopathogenic fungus Metarhizium anisopliae produces the volatile compound phenylethyl alcohol (PEA) that causes behavioral avoidance in locusts. This is mediated by the locust odorant binding protein 11 (LmOBP11). Expression of LmOBP11 is induced by M. anisopliae infection and PEA treatment. LmOBP11 participates in insect detection of the fungal-produced PEA and avoidance of PEA-contaminated food, but the upregulation of LmOBP11 upon M. anisopliae infection negatively affects the insect immune responses to ultimately benefit successful mycosis by the pathogen. RNAi knockdown of LmOBP11 increases the production of antimicrobial peptides and enhances locust resistance to M. anisopliae infection, while reducing host antennal electrophysiological responses to PEA and locust avoidance of PEA treated food. Also, transcriptomic and gut microbiome analyses reveal microbiome dysbiosis and changes in host genes involved in behavior and immunity. These results are consistent with the elevated expression of LmOBP11 leading to enhanced volatile detection and suppression of immune responses. CONCLUSION: These findings suggest a crosstalk between olfaction and immunity, indicating manipulation of host OBPs as a novel target exploited by fungal pathogens to alter immune activation and thus promote the successful infection of the host.
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Gafanhotos , Metarhizium , Micoses , Animais , Odorantes , Insetos/microbiologia , Gafanhotos/microbiologia , Metarhizium/fisiologia , Imunidade InataRESUMO
Thioester-containing proteins (TEPs) are present in many animal species ranging from deuterostomes to protostomes, which emphasizes their evolutionary conservation and importance in animal physiology. Phylogenetically, insect TEPs share sequence similarity with mammalian α2-macroglobulin. Drosophila melanogaster is specifically considered a superb model for teasing apart innate immune processes. Here we review recent discoveries on the involvement of Drosophila TEPs in the immune response against bacterial pathogens, nematode parasites, and parasitoid wasps. This information generates novel insights into the role of TEPs as regulators of homeostasis in Drosophila and supports the complexity of immune recognition and specificity in insects and more generally in invertebrates. These developments together with recent advances in gene editing and multi-omics will enable the fly immunity community to appreciate the molecular and mechanistic contributions of TEPs to the modulation of the host defense against infectious disease and possibly to translate this information into tangible therapeutic benefits.
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Drosophila melanogaster , Drosophila , Animais , Multiômica , Imunidade , MamíferosRESUMO
Insects constitute approximately 75% of the world's recognized fauna, with the majority of species considered as pests. Entomopathogenic fungi (EPF) are parasitic microorganisms capable of efficiently infecting insects, rendering them potent biopesticides. In response to infections, insects have evolved diverse defense mechanisms, prompting EPF to develop a variety of strategies to overcome or circumvent host defenses. While the interaction mechanisms between EPF and insects is well established, recent findings underscore that their interplay is more intricate than previously thought, especially evident across different stages of EPF infection. This review primarily focuses on the interplay between EPF and the insect defense strategies, centered around three infection stages: (1) Early infection stage: involving the pre-contact detection and avoidance behavior of EPF in insects, along with the induction of behavioral responses upon contact with the host cuticle; (2) Penetration and intra-hemolymph growth stage: involving the initiation of intricate cellular and humoral immune functions in insects, while symbiotic microbes can further contribute to host resistance; (3) Host insect's death stage: involving the ultimate confrontation between pathogens and insects. Infected insects strive to separate themselves from the healthy population, while pathogens rely on the infected insects to spread to new hosts. Also, we discuss a novel pest management strategy underlying the cooperation between EPF infection and disturbing the insect immune system. By enhancing our understanding of the intricate interplay between EPF and the insect, this review provides novel perspectives for EPF-mediated pest management and developing effective fungal insecticides.
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Cognição , Insetos , Animais , Hemolinfa , FungosRESUMO
Steinernema carpocapsae is an entomopathogenic nematode (EPN) that rapidly infects and kills a wide range of insect hosts and has been linked to host immunosuppression during the initial stages of infection. The lethal nature of S. carpocapsae infections has previously been credited to its symbiotic bacteria; however, it has become evident that the nematodes are able to effectively kill their hosts independently through their excretion/secretion products (ESPs). Here we examined how the adult Drosophila melanogaster immune system is modulated in response to S. carpocapsae ESPs in an attempt to ascertain individual pathogenic contributions of the isolated compound. We found that the S. carpocapsae ESPs decrease the survival of D. melanogaster adult flies, they induce the expression of certain antimicrobial peptide-encoding genes, and they cause significant reduction in phenoloxidase enzyme activity and delay in the melanization response in males flies. We also report that S. carpocapsae ESPs affect hemocyte numbers in both male and female individuals. Our results indicate the manipulative role of EPN ESPs and reveal sex-specific differences in the host response against nematode infection factors. These findings are beneficial as they promote our understanding of the molecular basis of nematode pathogenicity and the parasite components that influence nematode-host interactions.