Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Viral replication in the respiratory tract induces the death of infected cells and the release of pathogen- associated molecular patterns (PAMPs). PAMPs give rise to local inflammation, increasing the secretion of pro- inflammatory cytokines and chemokines, which attract immune cells from the blood into the infected lung. In most individuals, lung-recruited cells clear the infection, and the immune response retreats. However, in some cases, a dysfunctional immune response occurs, which triggers a cytokine storm in the lung, leading to acute respiratory distress syndrome (ARDS). Severe COVID-19 is characterized by an impaired innate and adaptive immune response and by a massive expansion of myeloid-derived suppressor cells (MDSCs). MDSCs function as protective regulators of the immune response, protecting the host from over-immunoreactivity and hyper-inflammation. However, under certain conditions, such as chronic inflammation and cancer, MDSCs could exert a detrimental role. Accordingly, the early expansion of MDSCs in COVID-19 is able to predict the fatal outcome of the infection. Here, we review recent data on MDSCs during COVID-19, discussing how they can influence the course of the disease and whether they could be considered as biomarker and possible targets for new therapeutic approaches.

Emerging viral infections in immunocompromised patients: A great challenge to better define the role of immune response

“…The inflammatory/suppressive signals in TME promote the recruitment and expansion of several type of immunosuppressive cells such as myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) or Treg responsible for the strong inhibition of the host immune response ( 27 – 29 ). A similar suppressor cell expansion as well the increase in the neutrophil/lymphocyte ratio that characterize cancer patients ( 30 ) was also observed during viral emerging infection such as COVID-19 ( 31 , 32 ). Their effects in dampening both antiviral and antitumoral immunity can therefore be exacerbated in cancer patients experiencing emerging infections.…”

Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and possible Treatments: All options on the Table

“…Another crucial issue in the pathogenesis and vaccination of COVID-19, which is related to CCL2, is the increase in the frequency of monocytic myeloid-derived suppressor cells (M−MDSCs) and the recruitment of these cells, which disrupt the host’s antiviral responses in a chronic inflammation condition. On the other hand, how MDSCs influence immunization following COVID-19 vaccination remains to be determined [138] . An investigation reported that the number of M−MDSCs was significantly higher in the blood of patients with severe COVID-19 than in control subjects.…”

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19

“…Increased levels of Arg-1 and ROS can further be observed in AP patients, especially those with a severe clinical course [ 174 ]. Similarly, expansion of M-MDSCs was reported together with increased Arg-1 activity in plasma, and these are associated with severity and fatal outcome in COVID-19 patients [ 175 ].…”

“…A proportion of circulating HLA-DR −/low monocytes seen in both AP and COVID-19 patients have been identified as CD14 + CD11b + HLA-DR −/low CD15 − monocytic myeloid-derived suppressor cells (M-MDSCs); these cell types may cloud earlier studies on the topic, as they could be misidentified as HLA-DR −/low classical monocytes [ 174 , 175 , 176 ]. M-MDSCs are characterized by their potent immunosuppressive effects on other immune cells, especially T cells, through various mechanisms including secretion of arginase-1 (Arg-1), and inducible nitric oxide synthase, production of reactive oxygen and nitrogen species, secretion of cytokines including TGF-β and IL-10, and induction of regulatory T cells [ 175 ].…”