Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response

Weavers, Helen; Evans, Iwan Robert; Martin, Paul; Wood, Will

doi:10.1016/j.cell.2016.04.049

Cited by 171 publications

(217 citation statements)

References 64 publications

(90 reference statements)

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“…A possible explanation for this discrepancy would be that hemocytes may differ in their expression profile, behavior, and phagocytic ability at various developmental stages due to differences in their microenvironment and/or sensitivity to stimuli. Accordingly, it has recently been shown that the phagocytic activity of embryonic hemocytes acts as a priming mechanism, increasing the ability of primed cells to phagocytose bacteria at later stages [78]. It is therefore possible that embryonic, larval and adult hemocytes display very different levels of priming and bacterial phagocytic activity, and that crq is required mostly in larval/adult bacterial phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging

et al. 2016

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Phagocytosis is an ancient mechanism central to both tissue homeostasis and immune defense. Both the identity of the receptors that mediate bacterial phagocytosis and the nature of the interactions between phagocytosis and other defense mechanisms remain elusive. Here, we report that Croquemort (Crq), a Drosophila member of the CD36 family of scavenger receptors, is required for microbial phagocytosis and efficient bacterial clearance. Flies mutant for crq are susceptible to environmental microbes during development and succumb to a variety of microbial infections as adults. Crq acts parallel to the Toll and Imd pathways to eliminate bacteria via phagocytosis. crq mutant flies exhibit enhanced and prolonged immune and cytokine induction accompanied by premature gut dysplasia and decreased lifespan. The chronic state of immune activation in crq mutant flies is further regulated by negative regulators of the Imd pathway. Altogether, our data demonstrate that Crq plays a key role in maintaining immune and organismal homeostasis.

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Section: Discussionmentioning

confidence: 99%

The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging

et al. 2016

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“…The process of macrophage “priming” or “training” occurs when prior exposure to a specific stimulus induces an enhanced immune response, such as increased microbicidal activity (i.e., increased phagocytic activity and increased expression of pro-inflammatory genes) [58]. As examples, stimuli that trigger priming can include phagocytosis of apoptotic cells [59], ingestion of ß-glucan (present in the Candida cell wall) [60], or exposure to lipopolysaccharide (LPS) [61]. In addition to altering gene expression, these stimuli can induce changes in metabolic function, such as triggering macrophages to switch to glucose metabolism to increase energy production for supporting increased cellular activation [62].…”

Section: Text Of the Reviewmentioning

confidence: 99%

Transfusion-related immunomodulation: a reappraisal

Youssef¹,

Spitalnik

2017

Current Opinion in Hematology

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Purpose of Review This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing “pure” red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the “storage lesion.” Macrophages are a key cell type involved in physiological and pathological RBC clearance and iron recycling. The plasticity and diversity of macrophages makes these cells potential mediators of immune suppression that could constitute TRIM. Recent Findings Recent reports identified the capacity of macrophages and monocytes to exhibit “memory.” Exposure to various stimuli, such as engulfment of apoptotic cells and interactions with ß-glucan and lipopolysaccharide, were found to induce epigenetic, metabolic, and functional changes in certain myeloid cells, particularly macrophages and monocytes. Summary Macrophages may mediate the immunosuppressive aspects of TRIM that arise as a result of transfused RBCs and their storage lesion induced by-products.

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“…Our data indicates that K63-polyubiquitylation on phagosomal 340 proteins is also used as a scaffold for the recruitment of signalling complexes, in particular the kinase complex TAK1/MKK7/JNK to MSR1 via specific polyubiquitylation on a conserved lysine K27. Remarkably, we could show that only MKK7 and not MKK4 2018; tissue damage and that this priming and subsequent recruitment to wounds was dependent on JNK (Weavers et al, 2016). This suggests that JNK activation induced by uptake of apoptotic bodies could regulate various responses.…”

Section: Ligases (Bilkei-gorzo Et Al Unpublished Data)mentioning

confidence: 54%

Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages

Guo

Härtlová

Prescott

et al. 2018

Preprint

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SummaryAlternatively activated M2 macrophages play an important role in maintenance of tissue homeostasis by scavenging dead cells, cell debris and lipoprotein aggregates via phagocytosis. Using proteomics, we investigated how alternative activation, driven by IL-4, modulated the phagosomal proteome to control macrophage function. Our data indicate that alternative activation enhances homeostatic functions such as proteolysis, lipolysis and nutrient transport. Intriguingly, we identified the enhanced recruitment of the TAK1/MKK7/JNK signalling complex to phagosomes of IL-4 activated macrophages. The recruitment of this signalling complex was mediated through K63-polyubiquitylation of the macrophage scavenger receptor 1 (MSR1). Triggering of MSR1 in IL-4 activated macrophages leads to enhanced JNK activation, thereby promoting a phenotypic switch from an anti-inflammatory to a pro-inflammatory state, which was abolished upon MSR1 deletion or JNK inhibition. Moreover, MSR1 K63-polyubiquitylation correlated with the activation of JNK signalling in ovarian cancer tissue from human patients, suggesting that it may be relevant for macrophage phenotypic shift in vivo. Altogether, we identified that MSR1 signals through JNK via K63-polyubiquitylation and provide evidence for the receptor’s involvement in macrophage polarization.

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Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response

Cited by 171 publications

References 64 publications

The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging

The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging

Transfusion-related immunomodulation: a reappraisal

Triggering MSR1 promotes JNK-mediated inflammation in IL-4 activated macrophages

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