Functional analysis of monocyte subsets in surgical sepsis
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Updated: Aug 14, 2026
Characterization of Human Monocyte Subsets by Whole Blood Flow Cytometry Analysis
Published on: October 17, 2018
C Schinkel1, R Sendtner, S Zimmer
1Ludwig-Maximilians University Munich, Klinikum Grosshadern, Department of Surgery, Germany.
Background:
Sepsis still remains a major cause of death after surgery. Impaired monocyte (Mphi) function and disruption of monocyte (Mphi/T-cell interaction were shown to be crucial for the development of septic complications in these patients. It was the objective of the study to assess more insights in Mphi behavior in surgical sepsis by means of analysis of Fc receptor- and human leukocyte antigen DR (HLA-DR) expression in Mphi subsets, and to evaluate the kinetics of these changes.
Methods:
In a prospective study, 20 septic patients and 10 healthy control subjects were included. Peripheral Mphi were isolated on consecutive days after onset of sepsis, and FcR positive (FcR+) and negative (FcR-) subsets were separated by rosetting with antibody-coated human erythrocytes. Cell surface receptor expression and in vitro cytokine production were used to determine the clinical importance of these subsets.
Results:
A significant monocytosis (3.5-fold; p < 0.01) and suppression of HLA-DR receptor expression (35%, p < 0.01) which correlate with sepsis severity and outcome could be demonstrated. There was a significant increase of FcR+ subsets in sepsis compared with control subjects (60% vs. 24%; p < 0.05). In vitro stimulation of Mphi subsets and peripheral blood mononuclear cells revealed suppressed interferon-gamma synthesis (p < 0.05 up to 0.01) from day 1 to day 5, elevated neopterin release (p < 0.05) on day 14 and increased synthesis rates of proinflammatory cytokines (e.g., interleukin-1beta); p < 0.05) predominantly in FcR+ subsets.
Conclusions:
Sepsis results in a significant monocytosis and suppression of HLA-DR receptor expression, which are correlating with sepsis severity and outcome. A significant shift toward FcR+ Mphi subsets can be found. This subpopulation resembles the previously described "angry macrophage" that is characterized by high proinflammatory cytokine synthesis and suppressed antigen presentation and that contributes to a disruption of adequate Mphi/T-cell interaction, rendering the host anergic toward opportunistic infections. The extend of HLA-DR suppression and the shift toward FcR+ Mphi might characterize a high risk patient subpopulation, which could benefit from immunomodulatory strategies.
Insights
Sepsis causes increased monocytes and reduced HLA-DR, correlating with severity. A shift to FcR+ macrophages, characterized by high cytokine production and suppressed antigen presentation, indicates a high-risk group potentially benefiting from immunomodulation.
Area of Science:
- Immunology
- Sepsis Pathophysiology
- Macrophage Biology
Background:
- Sepsis remains a leading cause of surgical mortality.
- Impaired monocyte function and T-cell interactions are critical in sepsis development.
- Understanding monocyte behavior in surgical sepsis is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate monocyte (Mphi) behavior in surgical sepsis.
- To analyze Fc receptor (FcR) and human leukocyte antigen DR (HLA-DR) expression in Mphi subsets.
- To evaluate the kinetics of these changes in relation to sepsis severity and outcome.
Main Methods:
- Prospective study including 20 septic patients and 10 healthy controls.
- Isolation of peripheral Mphi and separation into FcR+ and FcR- subsets.
- Assessment of cell surface receptor expression and in vitro cytokine production.
Main Results:
- Significant monocytosis (3.5-fold increase) and suppressed HLA-DR expression (35% reduction) observed in septic patients.
- Increased proportion of FcR+ Mphi subsets (60% vs. 24% in controls).
- Suppressed interferon-gamma synthesis, elevated neopterin, and increased pro-inflammatory cytokine production, particularly in FcR+ subsets.
Conclusions:
- Sepsis induces monocytosis and HLA-DR suppression, correlating with severity and outcome.
- A shift towards FcR+ Mphi subsets, termed 'angry macrophages,' is observed.
- These findings suggest a high-risk patient subpopulation that may benefit from immunomodulatory therapies.
