Analysis of Monocytic and Granulocytic Myeloid-Derived Suppressor Cells Subsets in Patients with Hepatitis C Virus Infection and Their Clinical Significance

Abstract

Myeloid-derived suppressor cells (MDSCs) have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV) infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs) in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+HLA-DR−/low cells (M-MDSCs) from HCV infected patients (mean ± SE, 3.134% ± 0.340%) was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461%) (Z = −2.438, P = 0.015), while there was no statistical difference between the frequency of HLA-DR−/lowCD33+CD11b+CD15+ (G-MDSCs) of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05), which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003); patients older than 40 years old group (mean ± SE, 3.673% ± 0.456%) had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482%) (Z = −2.685, P = 0.007). The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the level of liver inflammation degree.

The Role of Myeloid-Derived Suppressor Cells in Viral Infection

“…It will be important to determine whether different subsets of MDSCs (or other myeloid cells) infiltrate to different sites of infection or in response to different HSV species. (106,128).…”

Expansion of HLA-G-Expressing Myeloid-Derived Suppressor Cells in Patients with Chronic Hepatitis B Virus Infection

“…A study by Nonnenmann et al [38] reported that peripheral MDSCs were not significantly increased in patients with chronic HCV infection, and there was no difference in MDSC based on genotype or viral load, and a similar effect was found for suppression the function of CD8 + T cells. In another study, mMDSCs were observed to be unrelated to HCV RNA loads, and levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) [39].…”

“…The discrepancy might be explained by the differences in viral factors among different viral isolates or virally derived factors in generation and accumulation of MDSCs over the course of infection, or even by the influence of host genetic background and/or environmental differences. In this regard, Ning et al [39] reported that the frequency of mMDSCs in HCV infected patients had certain relevance with age, where patients older than 40 years old group had a significantly higher frequency of mMDSCs than that of age less than 40 years old group. In our study, however, we found that the frequency of gMDSCs was significantly higher in male than that in female HBV infected patients.…”

The role of myeloid-derived suppressor cells in chronic infectious diseases and the current methodology available for their study

“…[73][74][75][76][77] One study reported that M-MDSCs (CD14 + HLA-DR −/low ), but not G-MDSCs (HLA-DR −/low CD33 + CD11b + CD15 + ) from blood of HCV-infected subjects increased considerably in comparison with healthy controls. 78 Similarly, M-MDSCs increase significantly in blood of HIV/HCV-coinfected patients. 79 As in HIV, the viral HCV core protein (HCVc) could be involved in the induction of MDSC proliferation.…”

“…Several studies have reported an increase in MDSC levels in subjects positive for HCV . One study reported that M‐MDSCs (CD14 + HLA‐DR −/low ), but not G‐MDSCs (HLA‐DR −/low CD33 + CD11b + CD15 + ) from blood of HCV‐infected subjects increased considerably in comparison with healthy controls . Similarly, M‐MDSCs increase significantly in blood of HIV/HCV‐co‐infected patients …”