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Critical Care
Published in: Critical Care 4/2009

Open Access 01-08-2009 | Research

Phenotype changes and impaired function of dendritic cell subsets in patients with sepsis: a prospective observational analysis

Authors: Holger Poehlmann, Joerg C Schefold, Heidrun Zuckermann-Becker, Hans-Dieter Volk, Christian Meisel

Published in: Critical Care | Issue 4/2009

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Abstract

Introduction

Patients with sepsis often demonstrate severely impaired immune responses. The hallmark of this state of immunoparalysis is monocytic deactivation characterized by decreased human leukocyte antigen (HLA)-DR expression and reduced production of proinflammatory cytokines. Recently, diminished numbers of dendritic cells (DCs) were reported in patients with sepsis. However, little is known about DC phenotype and function in human sepsis. We therefore compared phenotypic and functional changes in monocyte and DC subsets in patients with sepsis and immunoparalysis.

Methods

In a prospective observational analysis, 16 consecutive patients with severe sepsis and septic shock (age 59.2 ± 9.7 years, 13 male, Sequential Organ Failure Assessment score 6.1 ± 2.7) and immunoparalysis (monocytic HLA-DR expression < 5,000 antibodies/cell) and 16 healthy volunteers were included. Peripheral blood DC counts, HLA-DR expression and ex vivo cytokine production were evaluated in comparison with monocyte subsets over time.

Results

At baseline, a profound reduction in the numbers of myeloid DCs (MDCs), plasmacytoid DCs (PDCs), and CD14dimCD16positive monocytes was observed in sepsis whereas CD14brightCD16negative and CD14brightCD16positive monocyte numbers were increased. HLA-DR expression was reduced on all monocyte and DC subsets. Production of proinflammatory cytokines and intracellular cytokine staining in response to lipopolysaccharide and lipoteichoic acid was impaired in monocyte subsets and MDCs, whereas IL-10 secretion was increased. IFNα response by stimulated PDCs was significantly decreased compared with controls. At day 28, HLA-DR expression and cytokine production of DC and monocyte subsets remained lower in septic patients compared with controls.

Conclusions

In sepsis, long-lasting functional deactivation is common to all circulating monocyte and DC subsets. In addition to decreased peripheral blood DC counts, functional impairment of antigen-presenting cells may contribute to an impaired antimicrobial defense in sepsis.
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Metadata
Title
Phenotype changes and impaired function of dendritic cell subsets in patients with sepsis: a prospective observational analysis
Authors
Holger Poehlmann
Joerg C Schefold
Heidrun Zuckermann-Becker
Hans-Dieter Volk
Christian Meisel
Publication date
01-08-2009
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2009
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7969

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