MDSCs in infectious diseases: regulation, roles, and readjustment

Abstract

Many pathogens, ranging from viruses to multicellular parasites, promote expansion of MDSC, which are myeloid cells that exhibit immunosuppressive features. The roles of MDSC in infection depend on the class and virulence mechanisms of the pathogen, the stage of the disease and the pathology associated with the infection. This work compiles evidence supported by functional assays on the roles of different subsets of MDSC in acute and chronic infections, including pathogen-associated malignancies, and discusses strategies to modulate MDSC dynamics in order to benefit the host.

The Engagement Between MDSCs and Metastases: Partners in Crime

“…Myeloid-derived suppressor cells (MDSCs) are a heterogeneous myeloid cell population characterized by immune regulatory properties (21,22). The differentiation and accumulation of MDSCs in human beings depends on pathological conditions such as cancer (23), infection (24), autoimmunity (25) and transplantation (26) but occurs during physiological processes such as aging (27) and pregnancy (28). MDSCs can be divided at least in three main subgroups according to the expression of selective surface markers: monocytic MDSC (M-MDSCs), that are characterized as CD11b + Ly6C + Ly6G − cells in mouse and CD11b + CD14 + CD15 − HLA-DR low/− CD124 + cells in human; polymorphonuclear-MDSC (PMN-MDSCs), that are identified as CD11b + Ly6C − Ly6G + cells in tumor-bearing mice and CD11b + CD14 − CD15 + HLA-DR low/− CD124 + cells in cancer patients (when the analysis is performed in low density mononuclear cell fraction); finally, the last MDSC subset is composed by "early immature" MDSCs (eMDSCs) defined as CD11b + Gr1 + CCR2 + Sca1 + CD31 + cells in mouse and Lin − CD11b + CD34 + CD33 + CD117 + HLA-DR low/− cells in human (8,21,29).…”

Target the Host, Kill the Bug; Targeting Host Respiratory Immunosuppressive Responses as a Novel Strategy to Improve Bacterial Clearance During Lung Infection

“…Chemotherapeutic drugs that target MDSCs could potentially be used in combination with standard antibiotic treatments to improve the immune response against chronic pulmonary bacterial infections. All-trans retinoic acid (ATRA) is an approved anti-cancer treatment, which leads to the maturationinduced ablation of MDSCs that often infiltrate tumors (194,195). Ablation of MDSCs in a murine model of tuberculosis was carried out using ATRA treatment (196).…”

Impact of infection on transplantation tolerance

“…106 For transplantation tolerance, perioperative recipient infusion of MDSCs has been shown to prolong allograft survival in mouse islet transplantation, 107 corneal transplantation 108 and skin transplantation. 110,111 On the other hand, we have recently shown that CMV infection in a murine model indeed impairs MDSC differentiation, thereby breaking transplantation tolerance mediated by MDSCs. On the one hand, both G-MDSCs and M-MDSCs have been shown to expand postinfection, which in turn inhibits subsequent T cell immune responses.…”

“…On the one hand, both G-MDSCs and M-MDSCs have been shown to expand postinfection, which in turn inhibits subsequent T cell immune responses. 110,111 On the other hand, we have recently shown that CMV infection in a murine model indeed impairs MDSC differentiation, thereby breaking transplantation tolerance mediated by MDSCs. 112 Acute CMV infection is found to inhibit G-MDSC expansion and impair the suppressive function of M-MDSCs.…”