Flow cytometric analysis of peripheral blood dendritic cells in patients with severe sepsis

Abstract

Background: Dendritic cells (DC) play a key role in cell-mediated immunity. We aimed to analyse the number and function of peripheral blood (PB) myeloid and plasmacytoid DC (mDC/pDC) in patients with severe sepsis.Methods: Twenty-six septic patients, 20 surgical patients (abdominal aortic aneurysm) and 20 healthy controls were enrolled in this prospective study.Results: At day 1 (enrollment in the study), septic patients showed in comparison with healthy controls, decreased mDC (P < 0.001) and increased pDC (P 5 0.03), resulting in a reduction of the mDC/ pDC ratio (P < 0.001). Surgery induced a decrease in both mDCs and pDCs level, without modification of mDC/pDC ratio. Septic patients included 15 survivors and 11 nonsurvivors. At day 1 no significant difference was found in mDC between the two groups, while pDCs were significantly higher in nonsurvivors (P 5 0.03). At the outcome, mDC were selectively increased with respect to day 1 in survivors (P 5 0.001), while no significant differences were observed as far as pDC count is concerned in both groups. Sorted DC from septic patients showed in comparison with healthy controls, reduced levels of HLA DR (P < 0.001), CD11c (P < 0.001), CD83 (P 5 0.006) and of costimulatory molecule CD86 (P 5 0.003); an up-regulation of chemokine receptor CXCR4 (P 5 0.031) and increased apoptosis (P < 0.001).Conclusions: Sepsis has a profound effect on PB DC compartment. These alterations appear to be sepsisspecific. Increased apoptosis and alteration of migration and trafficking mechanism may be involved in DC compartment modification. DC alterations could contribute to sepsis-mediated immunoparalysis. V C 2010 International Clinical Cytometry Society

Alterations of Dendritic Cells in Sepsis: Featured Role in Immunoparalysis

“…For two distinct populations of DCs, mDCs and pDCs, their numbers was markedly reduced in patients with sepsis when compared with controls, and both cell counts recovered slightly until day 28 [38]. But data from another clinical study of twenty-six patients showed that decreased mDC and increased pDC were observed at day 1, and the number of mDCs was not different in survivors and nonsurvivors of septic patients, while pDCs were obviously higher in nonsurvivors [39]. This discrepancy between these two study groups may be due to the different severity of illness.…”

“…At day 28, the expression of HLA-DR on mDCs was recovered but remained lower than that in controls, while HLA-DR on pDCs showed a similar expression pattern to controls [38]. Besides HLA-DR, the percentage of CD83 and CD86 was also reported to be reduced in septic patients, but chemokine receptor CXCR4 was upregulated [39]. …”

Septic Shock Sera Containing Circulating Histones Induce Dendritic Cell–Regulated Necrosis in Fatal Septic Shock Patients

“…In mouse models of SS, several studies have shown that DC numbers are decreased in the blood as well as the tissue level (8)(9)(10)(11)(12)(13)(14). Apoptosis has been proposed to be the main mechanism responsible for these observations (15).…”

Issue Highlights—January 2013

“…There is accumulating evidence that a diminished expression of human leukocyte antigen-DR on circulating monocytes (mHLA-DR) measured by flow cytometry is considered a reliable indicator of immunosuppression in critically ill patients (36,37). It is also known that monocytes with low HLA-DR expression are known to be unable to mount a proinflammatory response to any subsequent bacterial challenge or to properly present antigens to T cells (37).…”