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Updated: Feb 27, 2026
Pseudofracture: An Acute Peripheral Tissue Trauma Model
Published on: April 18, 2011
Phenotyping the Immune Response to Trauma: A Multiparametric Systems Immunology Approach
Anupamaa Seshadri1, Gabriel A Brat, Brian K Yorkgitis
1All authors: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Insights
Trauma alters immune cells, including increased Th17 CD4 T cells and expanded monocytes with reduced cytokine response. Monocyte innate functions like phagocytosis and oxidative burst were preserved post-injury.
Area of Science:
- Immunology
- Systems Biology
- Trauma Research
Background:
- Trauma triggers a complex immune response requiring systems biology approaches.
- Mass cytometry by time-of-flight (CyTOF) offers a novel high-dimensional platform for immune cell characterization.
Purpose of the Study:
- To comprehensively characterize the multicellular immune response to trauma using CyTOF.
- To identify time-dependent phenotypic changes in immune cell subsets following severe injury.
Main Methods:
- Peripheral blood mononuclear cells from trauma patients (n=10, ISS > 20) and controls were analyzed using CyTOF with 38-marker panels.
- Immune cell subsets were assessed for phenotypic changes, cytokine production, and monocyte function (phagocytosis, oxidative burst) at days 1, 3, and 5 post-injury.
Main Results:
- Trauma induced Th17-type CD4 T cell expansion with increased IL-17 and IL-22 expression by day 5.
- Natural killer (NK) cells showed decreased T-bet expression and reduced TNF-β, IFN-γ, and MCP-1.
- Monocytes expanded but exhibited decreased proinflammatory cytokine response and reduced HLA-DR expression, yet maintained phagocytosis and augmented oxidative burst.
Conclusions:
- CyTOF identified significant time-dependent immune cell alterations post-trauma, including Th17 induction, NK cell changes, and monocyte expansion with altered function.
- Despite reduced HLA-DR and cytokine response, monocyte innate antimicrobial functions (phagocytosis, oxidative burst) were preserved.
- Future studies will integrate CyTOF with RNAseq and functional assays to further elucidate trauma-induced immune cell subset changes.
Objective:
Trauma induces a complex immune response that requires a systems biology research approach. Here, we used a novel technology, mass cytometry by time-of-flight, to comprehensively characterize the multicellular response to trauma.
Design:
Peripheral blood mononuclear cells samples were stained with a 38-marker immunophenotyping cytometry by time-of-flight panel. Separately, matched peripheral blood mononuclear cells were stimulated in vitro with heat-killed Streptococcus pneumoniae or CD3/CD28 antibodies and stained with a 38-marker cytokine panel. Monocytes were studied for phagocytosis and oxidative burst.
Setting:
Single-institution level 1 trauma center.
Patients Or Subjects:
Trauma patients with injury severity scores greater than 20 (n = 10) at days 1, 3, and 5 after injury, and age- and gender-matched controls.
Interventions:
None.
Measurements And Main Results:
Trauma-induced expansion of Th17-type CD4 T cells was seen with increased expression of interleukin-17 and interleukin-22 by day 5 after injury. Natural killer cells showed reduced T-bet expression at day 1 with an associated decrease in tumor necrosis factor-β, interferon-γ, and monocyte chemoattractant protein-1. Monocytes showed robust expansion following trauma but displayed decreased stimulated proinflammatory cytokine production and significantly reduced human leukocyte antigen - antigen D related expression. Further analysis of trauma-induced monocytes indicated that phagocytosis was no different from controls. However, monocyte oxidative burst after stimulation increased significantly after injury.
Conclusions:
Using cytometry by time-of-flight, we were able to identify several major time-dependent phenotypic changes in blood immune cell subsets that occur following trauma, including induction of Th17-type CD4 T cells, reduced T-bet expression by natural killer cells, and expansion of blood monocytes with less proinflammatory cytokine response to bacterial stimulation and less human leukocyte antigen - antigen D related. We hypothesized that monocyte function might be suppressed after injury. However, monocyte phagocytosis was normal and oxidative burst was augmented, suggesting that their innate antimicrobial functions were preserved. Future studies will better characterize the cell subsets identified as being significantly altered by trauma using cytometry by time-of-flight, RNAseq technology, and functional studies.
