Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation

Introduction: Decreased expression of human leukocyte antigen class II (HLA-DR) on monocytes is a hallmark of altered immune status in patients with a systemic inflammatory response syndrome (SIRS). So far, the analyses were mainly performed without taking into account monocytes subpopulations. Methods: We studied this modification on CD14(HIGH) and CD14(LOW) monocytes of 20 SIRS patients undergoing abdominal aortic surgery (AAS), 20 patients undergoing carotid artery surgery (CAS), and 9 healthy controls, and we investigated mediators and intracellular molecules that may be involved in this process. Results: HLA-DR on CD14(HIGH) monocytes started to decrease during surgery, after blood reperfusion, and was further reduced post-surgery. In contrast, HLA-DR expression on CD14(LOW) cells only decreased after surgery, and to a lesser extent than on CD14(HIGH) monocytes. Negative correlations were found between the reduction of HLA-DR expression and the change in cortisol levels for both subpopulations, whereas a negative correlation between interleukin-10 (IL-10) levels and HLA-DR modulation was only observed for CD14(HIGH) cells. In accordance with these ex vivo results, HLA-DR on CD14(HIGH) and CD14(LOW) monocytes of healthy donors was reduced following incubation with hydrocortisone, whereas IL-10 only acted on CD14(HIGH) subpopulation. Furthermore, flow cytometry revealed that the expression of IL-10 receptor was higher on CD14(HIGH) versus CD14(LOW) monocytes. In addition, hydrocortisone, and to a lesser extent IL-10, reversed the up-regulation of HLA-DR induced by bacterial products. Finally, membrane-associated RING-CH-1 protein (MARCH1) mRNA, a negative regulator of MHC class II, was up-regulated in monocytes of AAS patients on Day 1 post-surgery, and in those of healthy subjects exposed to hydrocortisone. Conclusions: This study reveals that HLA-DR expression is modulated differently on CD14(HIGH) (classical) versus CD14(LOW) (inflammatory) monocytes after systemic inflammation.