Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles
Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying...
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| Format: | Article |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.621222/full |
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| author | Patrick P. G. Mulder Patrick P. G. Mulder Marcel Vlig Bouke K. H. L. Boekema Matthea M. Stoop Anouk Pijpe Paul P. M. van Zuijlen Paul P. M. van Zuijlen Paul P. M. van Zuijlen Paul P. M. van Zuijlen Evelien de Jong Evelien de Jong Bram van Cranenbroek Irma Joosten Hans J. P. M. Koenen Magda M. W. Ulrich Magda M. W. Ulrich |
| author_facet | Patrick P. G. Mulder Patrick P. G. Mulder Marcel Vlig Bouke K. H. L. Boekema Matthea M. Stoop Anouk Pijpe Paul P. M. van Zuijlen Paul P. M. van Zuijlen Paul P. M. van Zuijlen Paul P. M. van Zuijlen Evelien de Jong Evelien de Jong Bram van Cranenbroek Irma Joosten Hans J. P. M. Koenen Magda M. W. Ulrich Magda M. W. Ulrich |
| author_sort | Patrick P. G. Mulder |
| collection | DOAJ |
| description | Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1β, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1–2.8 × 106/ml after burn vs. 5 × 103/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4+ T cell population, elevated numbers of CCR4+CCR6- and CCR4+CCR6+ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications. |
| first_indexed | 2024-12-14T00:17:01Z |
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| id | doaj.art-860db79f6a4a4bf58b0f37822c72615e |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T00:17:01Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-860db79f6a4a4bf58b0f37822c72615e2022-12-21T23:25:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.621222621222Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine ProfilesPatrick P. G. Mulder0Patrick P. G. Mulder1Marcel Vlig2Bouke K. H. L. Boekema3Matthea M. Stoop4Anouk Pijpe5Paul P. M. van Zuijlen6Paul P. M. van Zuijlen7Paul P. M. van Zuijlen8Paul P. M. van Zuijlen9Evelien de Jong10Evelien de Jong11Bram van Cranenbroek12Irma Joosten13Hans J. P. M. Koenen14Magda M. W. Ulrich15Magda M. W. Ulrich16Preclinical Research, Association of Dutch Burn Centres (ADBC), Beverwijk, NetherlandsLaboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, NetherlandsPreclinical Research, Association of Dutch Burn Centres (ADBC), Beverwijk, NetherlandsPreclinical Research, Association of Dutch Burn Centres (ADBC), Beverwijk, NetherlandsBurn Center, Red Cross Hospital, Beverwijk, NetherlandsBurn Center, Red Cross Hospital, Beverwijk, NetherlandsBurn Center, Red Cross Hospital, Beverwijk, NetherlandsDepartment of Plastic and Reconstructive Surgery, Red Cross Hospital, Beverwijk, NetherlandsDepartment of Plastic, Reconstructive and Hand Surgery, Amsterdam Movement Sciences Amsterdam UMC, Location VUmc, Amsterdam, NetherlandsPediatric Surgical Centre, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Amsterdam, NetherlandsBurn Center, Red Cross Hospital, Beverwijk, NetherlandsDepartment of Intensive Care, Red Cross Hospital, Beverwijk, NetherlandsLaboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, NetherlandsLaboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, NetherlandsLaboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, NetherlandsPreclinical Research, Association of Dutch Burn Centres (ADBC), Beverwijk, NetherlandsDepartment of Plastic, Reconstructive and Hand Surgery, Amsterdam Movement Sciences Amsterdam UMC, Location VUmc, Amsterdam, NetherlandsSevere burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1β, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1–2.8 × 106/ml after burn vs. 5 × 103/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4+ T cell population, elevated numbers of CCR4+CCR6- and CCR4+CCR6+ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications.https://www.frontiersin.org/articles/10.3389/fimmu.2020.621222/fullimmune responseneutrophilsmonocyteslymphocytessystemicinflammation |
| spellingShingle | Patrick P. G. Mulder Patrick P. G. Mulder Marcel Vlig Bouke K. H. L. Boekema Matthea M. Stoop Anouk Pijpe Paul P. M. van Zuijlen Paul P. M. van Zuijlen Paul P. M. van Zuijlen Paul P. M. van Zuijlen Evelien de Jong Evelien de Jong Bram van Cranenbroek Irma Joosten Hans J. P. M. Koenen Magda M. W. Ulrich Magda M. W. Ulrich Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles Frontiers in Immunology immune response neutrophils monocytes lymphocytes systemic inflammation |
| title | Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles |
| title_full | Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles |
| title_fullStr | Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles |
| title_full_unstemmed | Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles |
| title_short | Persistent Systemic Inflammation in Patients With Severe Burn Injury Is Accompanied by Influx of Immature Neutrophils and Shifts in T Cell Subsets and Cytokine Profiles |
| title_sort | persistent systemic inflammation in patients with severe burn injury is accompanied by influx of immature neutrophils and shifts in t cell subsets and cytokine profiles |
| topic | immune response neutrophils monocytes lymphocytes systemic inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.621222/full |
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