The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury
Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the minutes, days and weeks following injury, damage...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1239683/full |
| _version_ | 1797742179046653952 |
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| author | Emily Horner Janet M. Lord Janet M. Lord Jon Hazeldine Jon Hazeldine |
| author_facet | Emily Horner Janet M. Lord Janet M. Lord Jon Hazeldine Jon Hazeldine |
| author_sort | Emily Horner |
| collection | DOAJ |
| description | Associated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the minutes, days and weeks following injury, damage associated molecular patterns (DAMPs) are a heterogeneous collection of proteins, lipids and DNA renowned for initiating the systemic inflammatory response syndrome. Suggesting additional immunomodulatory roles in the post-trauma immune response, data are emerging implicating DAMPs as potential mediators of post-trauma immune suppression. Discussing the results of in vitro, in vivo and ex vivo studies, the purpose of this review is to summarise the emerging immune tolerising properties of cytosolic, nuclear and mitochondrial-derived DAMPs. Direct inhibition of neutrophil antimicrobial activities, the induction of endotoxin tolerance in monocytes and macrophages, and the recruitment, activation and expansion of myeloid derived suppressor cells and regulatory T cells are examples of some of the immune suppressive properties assigned to DAMPs so far. Crucially, with studies identifying the molecular mechanisms by which DAMPs promote immune suppression, therapeutic strategies that prevent and/or reverse DAMP-induced immunosuppression have been proposed. Approaches currently under consideration include the use of synthetic polymers, or the delivery of plasma proteins, to scavenge circulating DAMPs, or to treat critically-injured patients with antagonists of DAMP receptors. However, as DAMPs share signalling pathways with pathogen associated molecular patterns, and pro-inflammatory responses are essential for tissue regeneration, these approaches need to be carefully considered in order to ensure that modulating DAMP levels and/or their interaction with immune cells does not negatively impact upon anti-microbial defence and the physiological responses of tissue repair and wound healing. |
| first_indexed | 2024-03-12T14:37:16Z |
| format | Article |
| id | doaj.art-7cd2a12febef453081bb81c019792ca2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T14:37:16Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7cd2a12febef453081bb81c019792ca22023-08-17T03:12:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12396831239683The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injuryEmily Horner0Janet M. Lord1Janet M. Lord2Jon Hazeldine3Jon Hazeldine4Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United KingdomInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, United KingdomNational Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham, United KingdomInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, United KingdomNational Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham, United KingdomAssociated with the development of hospital-acquired infections, major traumatic injury results in an immediate and persistent state of systemic immunosuppression, yet the underlying mechanisms are poorly understood. Detected in the circulation in the minutes, days and weeks following injury, damage associated molecular patterns (DAMPs) are a heterogeneous collection of proteins, lipids and DNA renowned for initiating the systemic inflammatory response syndrome. Suggesting additional immunomodulatory roles in the post-trauma immune response, data are emerging implicating DAMPs as potential mediators of post-trauma immune suppression. Discussing the results of in vitro, in vivo and ex vivo studies, the purpose of this review is to summarise the emerging immune tolerising properties of cytosolic, nuclear and mitochondrial-derived DAMPs. Direct inhibition of neutrophil antimicrobial activities, the induction of endotoxin tolerance in monocytes and macrophages, and the recruitment, activation and expansion of myeloid derived suppressor cells and regulatory T cells are examples of some of the immune suppressive properties assigned to DAMPs so far. Crucially, with studies identifying the molecular mechanisms by which DAMPs promote immune suppression, therapeutic strategies that prevent and/or reverse DAMP-induced immunosuppression have been proposed. Approaches currently under consideration include the use of synthetic polymers, or the delivery of plasma proteins, to scavenge circulating DAMPs, or to treat critically-injured patients with antagonists of DAMP receptors. However, as DAMPs share signalling pathways with pathogen associated molecular patterns, and pro-inflammatory responses are essential for tissue regeneration, these approaches need to be carefully considered in order to ensure that modulating DAMP levels and/or their interaction with immune cells does not negatively impact upon anti-microbial defence and the physiological responses of tissue repair and wound healing.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1239683/fullcritical caredamage associated molecular patternsimmunosuppressioninnate immunitytrauma |
| spellingShingle | Emily Horner Janet M. Lord Janet M. Lord Jon Hazeldine Jon Hazeldine The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury Frontiers in Immunology critical care damage associated molecular patterns immunosuppression innate immunity trauma |
| title | The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury |
| title_full | The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury |
| title_fullStr | The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury |
| title_full_unstemmed | The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury |
| title_short | The immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury |
| title_sort | immune suppressive properties of damage associated molecular patterns in the setting of sterile traumatic injury |
| topic | critical care damage associated molecular patterns immunosuppression innate immunity trauma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1239683/full |
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