Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster

Srinivasan, Naren; Gordon, Oliver; Ahrens, Susan; Franz, Anna; Deddouche, Safia; Chakravarty, Probir; Phillips, David H.; Yunus, Ali A.; Rosen, Michael K.; Valente, Rita S; Teixeira, Luı́s; Thompson, B. J.; Dionne, Marc S.; Wood, Will; Sousa, Caetano Reis e

doi:10.7554/elife.19662

Cited by 55 publications

(53 citation statements)

References 96 publications

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“…One might therefore anticipate that extracellular actin sensing preceded the evolution of adaptive immunity and constitutes an ancient mechanism for detecting tissue injury, with its roots perhaps in tissue repair. Consistent with that notion, actin injection into Drosophila melanogaster induces sterile JAK/STAT responses akin to ones previously seen in the context of injury or stress (Srinivasan et al , ). Interestingly, although there is no DNGR‐1 in Drosophila , the response requires the fly orthologues of Src and Syk arguing for possible evolutionary conservation of the pathway of extracellular actin detection (Srinivasan et al , ).…”

Section: Detecting Damagesupporting

confidence: 72%

Sensing infection and tissue damage

Sousa

2017

EMBO Mol Med

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Innate and adaptive immunity work concertedly in vertebrates to restore homoeostasis following pathogen invasion or other insults. Like all homoeostatic circuits, immunity relies on an integrated system of sensors, transducers and effectors that can be analysed in cellular or molecular terms. At the cellular level, T and B lymphocytes act as an effector arm of immunity that is mobilised in response to signals transduced by innate immune cells that detect a given insult. These innate cells are spread around the body and include dendritic cells (DCs), the chief immune sensors of pathogen invasion and tumour growth. At the molecular level, DCs possess receptors that directly sense pathogen presence and tissue damage and that signal via transduction pathways to control antigen presentation or regulate a plethora of genes encoding effector proteins that regulate immunity. Notably, molecular circuits for pathogen detection are not confined to DCs or even to immune cells. All cells express sensors and transducers that monitor invasion by viruses and bacteria and elicit suitable effector barriers to pathogen propagation. Here, I discuss work from my laboratory that has contributed to our understanding of these issues over the years.

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Section: Detecting Damagesupporting

confidence: 72%

Sensing infection and tissue damage

Sousa

2017

EMBO Mol Med

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“…In contrast, there is strong evidence of direct involvement of actin in invertebrate innate immunity. In Drosophila, extracellular actin triggers a response associated with wounding and dead cell clearance (Srinivasan et al, 2016). Actin-derived antimicrobial peptides have been identified in A. rubens (Maltseva et al, 2007), and extracellular actin has been shown to mediate antimicrobial defense in the mosquito Anopheles gambiae (Sandiford et al, 2015).…”

Section: Actin-binding Proteinsmentioning

confidence: 99%

Injury affects coelomic fluid proteome of the common starfishAsterias rubens

Shabelnikov

Bobkov

Sharlaimova

et al. 2019

Journal of Experimental Biology

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Echinoderms, possessing outstanding regenerative capabilities, provide a unique model system for the study of response to injury. However, little is known about the proteomic composition of coelomic fluid, an important biofluid circulating throughout the animal's body and reflecting the overall biological status of the organism. In this study, we used LC-MALDI tandem mass spectrometry to characterize the proteome of the cell-free coelomic fluid of the starfish Asterias rubens and to follow the changes occurring in response to puncture wound and blood loss. In total, 91 proteins were identified, of which 61 were extracellular soluble and 16 were bound to the plasma membrane. The most represented functional terms were 'pattern recognition receptor activity' and 'peptidase inhibitor activity'. A series of candidate proteins involved in early response to injury was revealed. Ependymin, β-microseminoprotein, serum amyloid A and avidin-like proteins, which are known to be involved in intestinal regeneration in the sea cucumber, were also identified as injuryresponsive proteins. Our results expand the list of proteins potentially involved in defense and regeneration in echinoderms and demonstrate dramatic effects of injury on the coelomic fluid proteome.

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“…Actin exists in a balance between monomeric and filamentous forms, and acts as a damage‐associated molecular pattern. Circulating actin was detected in patients with severe burns for up to 28 days after injury.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury

Dinsdale

Hazeldine

Tarrah

et al. 2019

British Journal of Surgery

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Background Circulating cell‐free DNA (cfDNA) is not found in healthy subjects, but is readily detected after thermal injury and may contribute to the risk of multiple organ failure. The hypothesis was that a postburn reduction in DNase protein/enzyme activity could contribute to the increase in cfDNA following thermal injury. Methods Patients with severe burns covering at least 15 per cent of total body surface area were recruited to a prospective cohort study within 24 h of injury. Blood samples were collected from the day of injury for 12 months. Results Analysis of blood samples from 64 patients revealed a significant reduction in DNase activity on days 1–28 after injury, compared with healthy controls. DNase protein levels were not affected, suggesting the presence of an enzyme inhibitor. Further analysis revealed that actin (an inhibitor of DNase) was present in serum samples from patients but not those from controls, and concentrations of the actin scavenging proteins gelsolin and vitamin D‐binding protein were significantly reduced after burn injury. In a pilot study of ten military patients with polytrauma, administration of blood products resulted in an increase in DNase activity and gelsolin levels. Conclusion The results of this study suggest a novel biological mechanism for the accumulation of cfDNA following thermal injury by which high levels of actin released by damaged tissue cause a reduction in DNase activity. Restoration of the actin scavenging system could therefore restore DNase activity, and reduce the risk of cfDNA‐induced host tissue damage and thrombosis.

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Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster

Cited by 55 publications

References 96 publications

Sensing infection and tissue damage

Sensing infection and tissue damage

Injury affects coelomic fluid proteome of the common starfishAsterias rubens

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury

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