Burn-Induced Local and Systemic Immune Response: Systematic Review and Meta-Analysis of Animal Studies

Mulder, Patrick P. G.; Koenen, Hans J. P. M.; Vlig, Marcel; Joosten, Irma; Vries, Rob B. M. de; Boekema, B.K.H.L.

doi:10.1016/j.jid.2022.05.004

Cited by 18 publications

(22 citation statements)

References 272 publications

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“…This can also be observed in the circulation of burn patients, where high levels of neutrophils were accompanied by high levels of IL-8 and MCP1, especially early after injury ( 8 ). Other studies have also shown that burn tissue contains large numbers of neutrophils in both human ( 37 ) and animals ( 14 , 38 ). The vast majority of neutrophils that infiltrated the wound area were mature, whereas, in peripheral blood from severely burned patients high numbers of immature neutrophils were detected ( 8 ).…”

Section: Discussionmentioning

confidence: 93%

“…age, sex and co-morbidities) ( 13 ). Moreover, present evidence on the processes that underlie burn injury originates mostly from animal research ( 14 ), which is only partially translatable to the human situation ( 15 ). We previously showed that in blood from severely burned patients, there was an extreme increase in innate immune cells and pro-inflammatory cytokines ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

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Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines

Mulder

Vlig²,

Fasse³

et al. 2022

Front. Immunol.

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The systemic and local immune response in burn patients is often extreme and derailed. As excessive inflammation can damage healthy tissues and slow down the healing process, modulation of inflammatory responses could limit complications and improve recovery. Due to its complexity, more detailed information on the immune effects of thermal injury is needed to improve patient outcomes. We therefore characterized and quantified subsets of immune cells and mediators present in human burn wound tissue (eschar), sampled at various time points. This study shows that after burn injury, the number of immune cells were persistently increased, unlike the normal wound healing process. There was an immediate, strong increase in neutrophils and a moderate increase in monocytes/macrophages and lymphocytes, especially in the second and third week post burn. The percentage of classical (CD14highCD16-) monocytes/macrophages demonstrated a steady decrease over time, whereas the proportion of intermediate (CD14highCD16+) monocytes/macrophages slowly increased. The absolute numbers of T cells, NK cells and B cells increased up to week 3, while the fraction of γδ T cells was increased only in week 1. Secretome profiling revealed high levels of chemokines and an overall pro-inflammatory cytokine milieu in burn tissue. The local burn immune response shows similarities to the systemic immune reaction, but differs in neutrophil maturity and lymphocyte composition. Altogether, the neutrophil surges, high levels of pro-inflammatory cytokines and limited immunosuppression might be key factors that prolong the inflammation phase and delay the wound healing process in burns.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines

Mulder

Vlig²,

Fasse³

et al. 2022

Front. Immunol.

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“…Research on cellular processes in burn wound healing is generally performed on animals [ 6 , 7 , 8 ]. Translation to the human situation is, however, difficult due to physiological differences between animals and humans [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, in our modern society we strive for innovative, animal-free ways of conducting research [ 11 ]. Human studies, on the other hand, are limited by the absence of baseline values, heterogeneity among patients, and restrictions in the collection of tissue samples [ 6 , 7 ]. Therefore, there is an important demand for alternative models to study burn injuries.…”

Section: Introductionmentioning

confidence: 99%

Full Skin Equivalent Models for Simulation of Burn Wound Healing, Exploring Skin Regeneration and Cytokine Response

Mulder

Raktoe

Vlig

et al. 2023

JFB

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Healing of burn injury is a complex process that often leads to the development of functional and aesthetic complications. To study skin regeneration in more detail, organotypic skin models, such as full skin equivalents (FSEs) generated from dermal matrices, can be used. Here, FSEs were generated using de-epidermalized dermis (DED) and collagen matrices MatriDerm® and Mucomaix®. Our aim was to validate the MatriDerm- and Mucomaix-based FSEs for the use as in vitro models of wound healing. Therefore, we first characterized the FSEs in terms of skin development and cell proliferation. Proper dermal and epidermal morphogenesis was established in all FSEs and was comparable to ex vivo human skin models. Extension of culture time improved the organization of the epidermal layers and the basement membrane in MatriDerm-based FSE but resulted in rapid degradation of the Mucomaix-based FSE. After applying a standardized burn injury to the models, re-epithelization occurred in the DED- and MatriDerm-based FSEs at 2 weeks after injury, similar to ex vivo human skin. High levels of pro-inflammatory cytokines were present in the culture media of all models, but no significant differences were observed between models. We anticipate that these animal-free in vitro models can facilitate research on skin regeneration and can be used to test therapeutic interventions in a preclinical setting to improve wound healing.

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“…It is known that the incidence of sepsis in burn patients, typically resulting from infection, is higher (8%–42.5%) than trauma (2.4%–16.9%) or even critical care patients (19%–38%) (Thompson, Zuniga, Sousse, Christy and Gurney 2022). Burn injuries can also increase a patient's susceptibility to infection by compromising their metabolic and immunological defenses (Jeschke, van Baar, Choudhry, Chung, Gibran and Logsetty 2020; Mulder, Koenen, Vlig, Joosten, de Vries and Boekema 2022). Also, burn injuries can expose large amount of nuclear materials, which might initiate a viral-like cellular response.…”

Section: Discussionmentioning

confidence: 99%

A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141-DCs as the key cellular components in septic prognosis

Qiao¹,

Wang²,

Xu³

et al. 2023

Preprint

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Differential body responses to various stresses, infectious or noninfectious, govern clinical outcomes ranging from asymptoma to death. However, the common molecular and cellular nature of the stress responsome across different stimuli is not described. In this study, we compared the expression behaviors between burns and COVID-19 infection by choosing the transcriptome of peripheral blood from related patients as the analytic target since the blood cells reflect the systemic landscape of immune homeostasis. We identified an immune co-stimulator (CD86)-centered network, named stress-response core (SRC), which coordinated multiple immune processes and was robust in membership and highly related to the clinical traits in both burns and COVID-19. An independent whole blood single-cell RNA sequencing of COVID-19 patients demonstrated that the monocyte-dendritic cell (Mono-DC) wing was the major cellular source of the SRC, among which the higher expression of the SRC in the monocyte was associated with the asymptomatic COVID-19 patients, while the quantity-restricted and function-defected CD1C-CD141- DCs were recognized as the key signature which linked to bad consequences in COVID-19. Specifically, the proportion of the CD1C-CD141- DCs and their SRC expression levels were step-wise reduced along with worse clinic conditions while the sub-cluster of CD1C-CD141- DCs of the critical COVID-19 patients was characterized of IFN signaling quiescence, high mitochondrial metabolism and immune-communication inactivation. Thus, our study identified an expression-synchronized and function-focused gene network which was decreased under burns and COVID-19 stress and argued the CD1C-CD141- DC as the prognosis-related cell population which might serve as a new target of diagnosis and therapy.

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Burn-Induced Local and Systemic Immune Response: Systematic Review and Meta-Analysis of Animal Studies

Cited by 18 publications

References 272 publications

Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines

Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines

Full Skin Equivalent Models for Simulation of Burn Wound Healing, Exploring Skin Regeneration and Cytokine Response

A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141-DCs as the key cellular components in septic prognosis

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