Myeloid-derived suppressor cells and vaccination against pathogens

Abstract

It is widely accepted that the immune system includes molecular and cellular components that play a role in regulating and suppressing the effector immune response in almost any process in which the immune system is involved. Myeloid-derived suppressor cells (MDSCs) are described as a heterogeneous population of myeloid origin, immature state, with a strong capacity to suppress T cells and other immune populations. Although the initial characterization of these cells was strongly associated with pathological conditions such as cancer and then with chronic and acute infections, extensive evidence supports that MDSCs are also involved in physiological/non-pathological settings, including pregnancy, neonatal period, aging, and vaccination. Vaccination is one of the greatest public health achievements and has reduced mortality and morbidity caused by many pathogens. The primary goal of prophylactic vaccination is to induce protection against a potential pathogen by mimicking, at least in a part, the events that take place during its natural interaction with the host. This strategy allows the immune system to prepare humoral and cellular effector components to cope with the real infection. This approach has been successful in developing vaccines against many pathogens. However, when the infectious agents can evade and subvert the host immune system, inducing cells with regulatory/suppressive capacity, the development of vaccines may not be straightforward. Notably, there is a long list of complex pathogens that can expand MDSCs, for which a vaccine is still not available. Moreover, vaccination against numerous bacteria, viruses, parasites, and fungi has also been shown to cause MDSC expansion. Increases are not due to a particular adjuvant or immunization route; indeed, numerous adjuvants and immunization routes have been reported to cause an accumulation of this immunosuppressive population. Most of the reports describe that, according to their suppressive nature, MDSCs may limit vaccine efficacy. Taking into account the accumulated evidence supporting the involvement of MDSCs in vaccination, this review aims to compile the studies that highlight the role of MDSCs during the assessment of vaccines against pathogens.

Local immune dysregulation and subsequent inflammatory response contribute to pulmonary edema caused by Enterovirus infection in mice

“…Under pathological conditions, MDSCs go to various organs and suppress T cells from exerting normal immune function through direct cell−cell contact or secretion of arginase-1 (Arg-1), inducible NO synthase (iNOS), and reactive oxygen species (ROS) factors. 34 Previously we found EVA71 enhanced iNOS expression in mice lungs. 35 Furthermore, some evidence suggests that the suppressive activity of MDSCs is through the expansion and activation of regulatory T cells.…”

“…To date, the role of MDSCs during CVA6 infection is not known. Under pathological conditions, MDSCs go to various organs and suppress T cells from exerting normal immune function through direct cell−cell contact or secretion of arginase‐1 (Arg‐1), inducible NO synthase (iNOS), and reactive oxygen species (ROS) factors 34 . Previously we found EVA71 enhanced iNOS expression in mice lungs 35 .…”

Immunomodulatory actions of myeloid-derived suppressor cells in the context of innate immunity

“…Moreover, understanding the mechanisms that may affect MDSCs following vaccination may lead to the development of more efficient vaccines in some cases. 49 , 50 During infections, their role has been reported as positive or negative as regards to the clinical outcomes, depending on the type and load of the pathogen and the condition of the host ( Figure 1 ). Ost et al reviewed the way that MDSCs act during infections by Staphylococcus aureus , Mycobacterium tuberculosis , Pseudomonas aeruginosa , Porphyromonas gingivalis and Klebsiella pneumonia.…”

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

“…Of great significance in severe COVID-19 and any other ARDS, a high NLR is a sign of, and is associated with, increased presence of myeloid derived suppressor cells, (MDSC). MDSC are an immunosuppressive neutrophil (or monocytic) subset that can damage T cells in their vicinity [ 31 , 32 ]. This is diagrammed in Figure 1 .…”