Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients

Abstract

Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC p < 0.001, mDC1 p < 0.001, mDC2 p = 0.005) and increased numbers of IRF8-positive monocytes (p < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections (p = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.

Keywords: dendritic cells; dialysis; infections; interferon regulatory factor 8 (IRF8); monocytes.

Figure 1

Changes in cell numbers of immune cell subsets comparing 79 dialysis patients with 44 healthy controls. **—p = 0.01; ****—p ≤ 0.0001; KFRT; kidney failure receiving replacement therapy; mDC, myeloid dendritic cells; NBD, normal blood donors; NK, natural killer; pDC, plasmacytoid dendritic cells.

Figure 2

Changes in IRF8 expression in dendritic cells and monocytes comparing 79 dialysis patients with 44 healthy controls. (A) Differences in counts of IRF8-positive dendritic cells and IRF8 expression in each dendritic cell between dialysis patients and control subjects. (B) Differences in counts of IRF8-positive monocytes and IRF8 expression in each monocyte between dialysis patients and control subjects. **—p = 0.01; ***—p = 0.001; ****—p ≤ 0.0001; KFRT; kidney failure receiving replacement therapy; gMFI, geometric mean; IRF8, interferon regulatory factor 8; mDC, myeloid dendritic cells; NBD, normal blood donors; pDC, plasmacytoid dendritic cells.

Figure 3

Impaired IFR8 expression in plasmacytoid dendritic cells is associated with an increased rate of infections requiring hospital admissions upon follow-up of one year after the FACS analysis. (A) Dialysis patients who experienced hospital treatment of infections within one year after the FACS measurement displayed lower IRF8 expression in plasmacytoid dendritic cells than patients without such episodes at the one-year follow-up (p = 0.04). (B) ROC analysis of IRF8 expression in plasmacytoid dendritic cells as a potential predictor for upcoming severe infections (AUC = 0.7, p = 0.04). (C) Infection-free survival dependent on IRF8 expression in plasmacytoid dendritic cells after dividing 75 dialysis patients into two equal groups according to the median IRF8 expression (p = 0.41).