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

Abstract

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.