Harnessing the natural Drosophila-parasitoid model for integrating insect immunity with functional venomics

Heavner, Mary Ellen; Hudgins, Adam D.; Rajwani, Roma; Morales, Jorge; Govind, Shubha

doi:10.1016/j.cois.2014.09.016

Cited by 10 publications

(9 citation statements)

References 55 publications

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“…Because of their key role in wasp parasitism of Drosophila spp. [4, 5], we hypothesized that differences in the composition of spiked particles produced in the venom of both wasps underlie these contrasting infection strategies.…”

Section: Resultsmentioning

confidence: 99%

Novel Organelles with Elements of Bacterial and Eukaryotic Secretion Systems Weaponize Parasites of Drosophila

et al. 2017

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SUMMARY The evolutionary success of parasitoid wasps, a highly diverse group of insects widely used in biocontrol, depends on a variety of life history strategies in conflict with those of their hosts [1]. Drosophila melanogaster is a natural host of parasitic wasps of the genus Leptopilina. Attack by L. boulardi (Lb), a specialist wasp to flies of the melanogaster group, activates NF-κB-mediated humoral and cellular immunity. Inflammatory blood cells mobilize and encapsulate Lb eggs and embryos [2–5]. L. heterotoma (Lh), a generalist wasp, kills larval blood cells and actively suppresses immune responses. Spiked virus-like particles (VLPs) in wasp venom have clearly been linked to its successful parasitism of Drosophila [6], but VLP composition and their biotic nature have remained mysterious. Our proteomics studies reveal that VLPs lack viral coat proteins but possess a pharmacopoeia of (a) eukaryotic vesicular transport system, (b) immunity, and (c) previously unknown proteins. These novel proteins distinguish Lh from Lb VLPs; notably, some proteins specific to Lh VLPs possess sequence similarities with bacterial secretion system proteins. Structure-informed analyses of an abundant Lh VLP surface/spike-tip protein, p40, reveal similarities to the needle-tip invasin proteins SipD/IpaD of Gram negative bacterial type 3 secretion systems that breach immune barriers and deliver virulence factors into mammalian cells. Our studies suggest that Lh VLPs represent a new class of extracellular organelles and share pathways for protein delivery with both eukaryotic microvesicles and bacterial surface secretion systems. Given their mixed prokaryotic/eukaryotic properties, we propose the term Mixed Strategy Extracellular Vesicles (MSEVs) to replace VLP.

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Section: Resultsmentioning

confidence: 99%

Novel Organelles with Elements of Bacterial and Eukaryotic Secretion Systems Weaponize Parasites of Drosophila

et al. 2017

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“…The advanced knowledge on Drosophila immunity is a great asset to decipher mechanisms ensuring parasitic success which, for Drosophila endoparasitoids, mainly relies on injection of venom containing immunosuppressive proteins (Poirié et al., 2014; Moreau and Asgari, 2015). The venom effect on the hemocytes, the lymph gland or the melanisation has been described for Leptopilina species (Dubuffet et al., 2009; Heavner et al., 2014). The Leptopilina and Ganaspis venom contains not only soluble proteins but also peculiar vesicles with an unclear biogenesis (Rizki and Rizki, 1990; Dubuffet et al., 2009; Ferrarese et al., 2009; Gatti et al., 2012), which are likely involved in parasitic success.…”

Section: How Parasitic Wasps Target the Drosophila Immune Systemmentioning

confidence: 99%

Drosophila Cellular Immunity Against Parasitoid Wasps: A Complex and Time-Dependent Process

Kim-Jo¹,

Gatti²,

Poirié³

2019

Front. Physiol.

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Host-parasitoid interactions are among the most studied interactions between invertebrates because of their fundamental interest – the evolution of original traits in parasitoids – and applied, parasitoids being widely used in biological control. Immunity, and in particular cellular immunity, is central in these interactions, the host encapsulation response being specific for large foreign bodies such as parasitoid eggs. Although already well studied in this species, recent data on Drosophila melanogaster have unquestionably improved knowledge of invertebrate cellular immunity. At the same time, the venomics of parasitoids has expanded, notably those of Drosophila . Here, we summarize and discuss these advances, with a focus on an emerging “time-dependent” view of interactions outcome at the intra- and interspecific level. We also present issues still in debate and prospects for study. Data on the Drosophila -parasitoid model paves the way to new concepts in insect immunity as well as parasitoid wasp strategies to overcome it.

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“…Their attack mechanisms range from biochemical warfare and mimicry, to passive evasion and active immune suppression [1][2][3]. Drosophila and their parasitic wasps are an emerging model for studying how wasps evade or suppress host defenses [4,5]. The generalist Leptopilina heterotoma (Lh) succeeds on the Drosophila species within and beyond the melanogaster group.…”

Section: Introductionmentioning

confidence: 99%

A parasitoid wasp of Drosophila employs preemptive and reactive strategies to deplete its host’s blood cells

2021

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The wasps Leptopilina heterotoma parasitize and ingest their Drosophila hosts. They produce extracellular vesicles (EVs) in the venom that are packed with proteins, some of which perform immune suppressive functions. EV interactions with blood cells of host larvae are linked to hematopoietic depletion, immune suppression, and parasite success. But how EVs disperse within the host, enter and kill hematopoietic cells are not well understood. Using an antibody marker for L. heterotoma EVs, we show that these parasite-derived structures are readily distributed within the hosts’ hemolymphatic system. EVs converge around the tightly clustered cells of the posterior signaling center (PSC) of the larval lymph gland, a small hematopoietic organ in Drosophila. The PSC serves as a source of developmental signals in naïve animals. In wasp-infected animals, the PSC directs the differentiation of lymph gland progenitors into lamellocytes. These lamellocytes are needed to encapsulate the wasp egg and block parasite development. We found that L. heterotoma infection disassembles the PSC and PSC cells disperse into the disintegrating lymph gland lobes. Genetically manipulated PSC-less lymph glands remain non-responsive and largely intact in the face of L. heterotoma infection. We also show that the larval lymph gland progenitors use the endocytic machinery to internalize EVs. Once inside, L. heterotoma EVs damage the Rab7- and LAMP-positive late endocytic and phagolysosomal compartments. Rab5 maintains hematopoietic and immune quiescence as Rab5 knockdown results in hematopoietic over-proliferation and ectopic lamellocyte differentiation. Thus, both aspects of anti-parasite immunity, i.e., (a) phagocytosis of the wasp’s immune-suppressive EVs, and (b) progenitor differentiation for wasp egg encapsulation reside in the lymph gland. These results help explain why the lymph gland is specifically and precisely targeted for destruction. The parasite’s simultaneous and multipronged approach to block cellular immunity not only eliminates blood cells, but also tactically blocks the genetic programming needed for supplementary hematopoietic differentiation necessary for host success. In addition to its known functions in hematopoiesis, our results highlight a previously unrecognized phagocytic role of the lymph gland in cellular immunity. EV-mediated virulence strategies described for L. heterotoma are likely to be shared by other parasitoid wasps; their understanding can improve the design and development of novel therapeutics and biopesticides as well as help protect biodiversity.

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Harnessing the natural Drosophila-parasitoid model for integrating insect immunity with functional venomics

Cited by 10 publications

References 55 publications

Novel Organelles with Elements of Bacterial and Eukaryotic Secretion Systems Weaponize Parasites of Drosophila

Novel Organelles with Elements of Bacterial and Eukaryotic Secretion Systems Weaponize Parasites of Drosophila

Drosophila Cellular Immunity Against Parasitoid Wasps: A Complex and Time-Dependent Process

A parasitoid wasp of Drosophila employs preemptive and reactive strategies to deplete its host’s blood cells

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