Diminished HLA-DR expression on monocyte and dendritic cell subsets indicating impairment of cellular immunity in pre-term neonates: a prospective observational analysis.

AIMS: The risk of neonates for severe infection/sepsis is reciprocally proportional to gestational age and birth weight. As monocytes and dendritic cells (DC) are recognised key antigen-presenting immune cells, we aimed to elucidate whether neonatal age is associated with reduced expression of human-leukocyte antigen-DR (HLA-DR) antigens on subsets of monocytes and DCs. METHODS: Forty-three consecutive neonates (20 male, mean gestational age 236.0±26.8 days; mean 1-min Apgar score 7.5±2.0) were included in a monocentric prospective observational analysis. Patients were grouped according to gestational age (n=15 full-term, n=28 pre-term defined as <33 weeks). Ten healthy adult volunteers were assessed also. Flow-cytometric assessment of HLA-DR expression was performed in subsets of peripheral blood myeloid and plasmacytoid DCs (MDC and PDC) and monocytes (CD14brightCD16negative/CD14positiveCD16positive/CD14dimCD16positive). Clinical and routine laboratory data were followed up. RESULTS: At birth, leukocyte counts were increased in full-term neonates. Monocyte counts were significantly increased in neonates when compared with adults (all P<0.05). A significant numerical increase of CD14brightCD16negative and CD14positiveCD16positive monocytes was noted in pre-term and full-term neonates (all P<0.05), while HLA-DR expression in these subsets was significantly diminished (most pronounced in pre-term infants, P<0.0001). MDC and PDC HLA-DR expression was reduced also (all P<0.05). Clinical indices (e.g., pH, days on antibiotics/mechanical ventilation, fever/sepsis) were not found to correlate with immunological indices. CONCLUSIONS: We observed a markedly diminished HLA-DR expression on monocyte and DC subsets in pre-term and full-term neonates, which may contribute to impaired antimicrobial defence mechanisms in the early days of life.

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

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. IFNalpha 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.