rat-burn-model-to-study-full-thickness-cutaneous-thermal-burn

Rat Burn Model to Study Full-Thickness Cutaneous Thermal Burn and Infection

Burn induction methodologies are inconsistently described in rat models. A uniform burn wound model, which represents the clinical scenario, is necessary ...

University of North Carolina School of Medicine

University of North Carolina at Chapel Hill

The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. Serum, spleen, and peripheral lymph nodes were harvested at 3 and 14 days after injury. Flow cytometry was performed to identify and characterize adaptive and innate cell compartments. Elevated proinflammatory and anti-inflammatory serum cytokines and profound leukopenia were observed after RCI. A population of cells with dual expression of the cell surface markers Gr-1 and CD11b were identified in all experimental groups, but were significantly elevated after burn alone and RCI at 14 days after injury. In contrast to the T-cell-suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon γ and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell-like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1CD11b cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host.

Radiation combined with thermal injury induces immature myeloid cells.

Burn injury induces an acute hyperactive immune response followed by a chronic immune dysregulation that leaves those afflicted susceptible to multiple secondary infections. Many murine models are able to recapitulate the acute immune response to burn injury, yet few models are able to recapitulate long-term immune suppression and thus chronic susceptibility to bacterial infections seen in burn patients. This has hindered the field, making evaluation of the mechanisms responsible for these susceptibilities difficult to study. Herein we describe a novel mouse model of burn injury that promotes chronic immune suppression allowing for susceptibility to primary and secondary infections and thus allows for the evaluation of associated mechanisms.

One-hit wonder: Late after burn injury, granulocytes can clear one bacterial infection but cannot control a subsequent infection.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

SARS-CoV-2 infection of the oral cavity and saliva.

No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, non-invasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients.

Early expression of IL-10, IL-12, ARG1 and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury.

Article	Year
Radiation combined with thermal injury induces immature myeloid cells. Shock (Augusta, Ga.)\| PubMed ID: 23042190	2012
One-hit wonder: Late after burn injury, granulocytes can clear one bacterial infection but cannot control a subsequent infection. Burns : journal of the International Society for Burn Injuries\| PubMed ID: 30833100	2019
SARS-CoV-2 infection of the oral cavity and saliva. Nature medicine\| PubMed ID: 33767405	2021
Early expression of IL-10, IL-12, ARG1 and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury. The journal of trauma and acute care surgery\| PubMed ID: 35363228	2022

Robert Maile

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