Transdifferentiation and Proliferation in Two Distinct Hemocyte Lineages in Drosophila melanogaster Larvae after Wasp Infection

Ines, Anderl; Vesala, Laura; Ihalainen, Teemu O.; Vanha-aho, Leena-Maija; Andó, István; Rämet, Mika; Hultmark, Dan

doi:10.1371/journal.ppat.1005746

Cited by 130 publications

(211 citation statements)

References 74 publications

(117 reference statements)

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“…Consequently, crystal cells need sessile plasmatocytes to be, themselves, sessile . Lamellocytes are barely present in healthy larvae, but can differentiate from plasmatocytes or prohaemocytes in response to specific stress signals, such as parasitization. They are thought to play an essential role in encapsulation of parasitoid wasp eggs.…”

Section: Resultsmentioning

confidence: 99%

Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

et al. 2019

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Eater and NimC1 are transmembrane receptors of the Drosophila Nimrod family, specifically expressed in haemocytes, the insect blood cells. Previous ex vivo and in vivoRNAi studies have pointed to their role in the phagocytosis of bacteria. Here, we have created a novel NimC1 null mutant to re‐evaluate the role of NimC1, alone or in combination with Eater, in the cellular immune response. We show that NimC1 functions as an adhesion molecule ex vivo, but in contrast to Eater it is not required for haemocyte sessility in vivo. Ex vivo phagocytosis assays and electron microscopy experiments confirmed that Eater is the main phagocytic receptor for Gram‐positive, but not Gram‐negative bacteria, and contributes to microbe tethering to haemocytes. Surprisingly, NimC1 deletion did not impair phagocytosis of bacteria, nor their adhesion to the haemocytes. However, phagocytosis of both types of bacteria was almost abolished in NimC11;eater1 haemocytes. This indicates that both receptors contribute synergistically to the phagocytosis of bacteria, but that Eater can bypass the requirement for NimC1. Finally, we uncovered that NimC1, but not Eater, is essential for uptake of latex beads and zymosan particles. We conclude that Eater and NimC1 are the two main receptors for phagocytosis of bacteria in Drosophila, and that each receptor likely plays distinct roles in microbial uptake.

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Section: Resultsmentioning

confidence: 99%

Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

et al. 2019

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“…We quantified free glycerol and all CCA substrates with the free glycerol reagent (F6428, Sigma) and the triglyceride reagent (TR, T2449, Sigma). Fat bodies from [15][16][17][18][19][20] wandering L3 larvae were dissected in water, heated to 70°C for 10 min and centrifuged for 2 min at 13000 RPM. Protein concentration was measured by colorimetric method (Pierce™…”

Section: Triglyceride Measurementsmentioning

confidence: 99%

“…When faced with infestation by parasitoid wasps, Drosophila larvae produce a third type of blood cells: the lamellocytes. These cell types differentiate from plasmatocytes [14] or hemocyte progenitors [15] and form a capsule around wasp eggs or intruders, which are too large to be phagocytosed.…”

Section: Introductionmentioning

confidence: 99%

Metabolic adjustment ofDrosophilahemocyte number and sessility by an adipokine

Ramond

Petrignani

Dudzic

et al. 2019

Preprint

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In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that the adipokine NimB5 is produced in the fat body upon nutrient scarcity downstream of metabolic sensors. NimB5 is then secreted and bind to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals. Short title: The adipokine NimrodB5 regulates peripheral hematopoiesis in Drosophila Author summaryDrosophila larval hemocytes (blood cells) are found in two compartments: the lymph gland considered as a reservoir, and the peripheral compartment. Peripheral hemocytes form sessile patches attached to the internal surface of the larval body wall or are found freely circulating in the hemolymph. Little is known about the signals that regulate hemocytes proliferation and localization in the peripheral compartment. In this study, we have identified a new gene, NimrodB5, coding for the NimB5 protein, which is secreted by the fat body and binds to hemocytes. NimB5 inhibits hemocyte proliferation while promoting sessility, leading to an increased number of circulating hemocytes and adhesion defects in NimB5 mutant. We show that nimrodB5 expression by the fat body is controlled by metabolic cues to adjust hemocyte number to the physiological state of the larvae.Interestingly, deregulation of NimB5 causes lethality when larvae are raised on a poor diet due to a defect in regulating hemocytes proliferation. In conclusion, we have identified a new adipokine that optimizes hemocytes number to the physiological state of larvae. Our study also reveals a major role of the fat body in peripheral hematopoiesis regulation and outline how it can be costly to maintain a basal immune defense.

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“…4B). The msn promoter is active in many lymph gland progenitors as early as 56 hours (second larval instar (40)) and given that the macrophage/lamellocyte lineages have a shared origin (33,41,42), we hypothesized that mutant blood cells influence systemic health of animals. Targeted knockdown (msn>STAT RNAi and even msn>spz RNAi ) in the overgrowing hop Tum-l blood cell population rescued metabolic inflammation in larval adipocytes (Fig.…”

Section: A Blood Cell-derived Signal Affects Metainflammation and Efomentioning

confidence: 99%

ADrosophilametainflammation-blood tumor model links aspirin-triggered eicosanoid-like mediators to immune signaling

Govind

Panettieri

Paddibhatla

et al. 2019

Preprint

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Accumulating data from epidemiologic studies are linking aspirin's use to a decline in chronic and metabolic inflammation that underlies many human diseases including some cancers. Aspirin reduces cyclooxygenase-mediated pro-inflammatory prostaglandins and promotes the production of pro-resolution molecules. Aspirin also triggers the production of anti-inflammatory electrophilic mono-oxygenated lipid mediators implicated in human pathologies. With the goal of developing a model system for studying the mechanisms of aspirin in reducing inflammation, we investigated aspirin's effects in fruit fly models of chronic inflammation. Ectopic Toll/NF-κB and JAK/STAT signaling in D. melanogaster results in an overproliferation of hematopoietic blood progenitors coupled with metabolic inflammation in adipocytes. We report that, like mammals, flies are sensitive to aspirin treatment and it modulates the Toll-NF-κB axis. Aspirin-treated mutants simultaneously experience reduction in metabolic inflammation, mitosis, ectopic immune signaling, and macrophage infiltration. Moreover, flies synthesize 13-HODE, and aspirin triggers 13-EFOX-L2 production in mutants. In such flies with ectopic immune signaling, providing 13-HODE's precursor linoleic acid or performing targeted knockdown of transcription factor STAT in inflammatory blood cells boosts 13-EFOX-L2 levels while decreasing metabolic inflammation. Thus, hematopoietic cells regulate metabolic inflammation in flies, and their effects can be reversed by pharmaceutical or dietary intervention, suggesting deep phylogenetic conservation in animals' ability to resolve systemic inflammation and repair tissue damage. This model system brings the power of Drosophila genetics to bear on immuno-metabolic mechanisms that boost systemic health and healing, with the potential to identify new targets for the treatment of chronic diseases in humans.

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Transdifferentiation and Proliferation in Two Distinct Hemocyte Lineages in Drosophila melanogaster Larvae after Wasp Infection

Cited by 130 publications

References 74 publications

Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

Metabolic adjustment ofDrosophilahemocyte number and sessility by an adipokine

ADrosophilametainflammation-blood tumor model links aspirin-triggered eicosanoid-like mediators to immune signaling

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