Myeloid-Derived Suppressor Cells in Microbial Infection

Myeloid-Derived Suppressor Cells (MDSC) were first described in 1978 as “natural suppressor cells” in the context of experimental systemic mycobacterial infection and subsequently as “immunosuppressive myeloid cells” that inhibited T-cell proliferation in a mouse model of lung cancer. As the field expanded, MDSC have been recognized as a major immune regulatory cell type, key mediators of immune resistance in cancer, and markers of clinical progression. Despite their heterogeneity and scantly defined developmental trajectories, the study of MDSC has provided clinically relevant information on tumor pathobiology and neoplastic progression. The roles of MDSC in infectious diseases are still elusive. Unlike cancer pathology, where MDSC are responsible for immune suppression, MDSC may play a dual role during infection. Due to high amounts of bactericidal molecules like ROS and iNOS, MDSC could restrict microbial invasion and control hyperinflammation, i.e., in polymicrobial sepsis and neonatal sepsis. However, MDSC could facilitate establishment and maintenance of an immune suppressive environment and may serve as reservoir for intracellular pathogens such as Mycobacterium tuberculosis.

Accumulation of MDSC is associated with chronic and acute inflammation by the action of growth factors (GF), such as vascular endothelial-GF (VEGF), granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (M-CSF), and stem cell factor (SCF), DAMPs (S100 calcium-binding protein A8/A9, S100A8/9), and possibly chemokines (CXCL1, CXCL2). According to their lineage and phenotype, MDSC in animals and humans may be categorized as polymorphonuclear (PMN)- or monocytic (M)-MDSC. In human, early-stage MDSC (E-MDSC) represent a third subset that is lineage negative (Lin-). In the absence of MDSC-specific markers to discern between MDSC and other myeloid cells, their identification requires confirmation of suppressive functions.

With this Research Topic, we aim at expanding the current understanding of the roles of these myeloid regulatory cells in microbial infection across the spectrum of microbial diseases, including bacterial, viral, and protozoan infection. We welcome the submission of Original Research, Review, Mini Review, Methods, Perspective, Clinical Trial, Case Reports, and Opinion articles that address, but are not limited to, the following topics:
• Origins of MDSC in infection
• Challenges in identifying and characterizing MDSC
• Novel markers discriminating MDSC from other myeloid cell populations in microbial infection
• Determinants of suppressive activity in infectious disease
• MDSC in neonatal infection/infections of the elderly
• MDSC as mediators of infectious outcome in immunocompromised individuals
• MDSC-mediated immune regulation in infectious disease
• MDSC as biomarkers of infection, disease, or resolution
• MDSC as therapeutic targets in infectious disease
• MDSC in vaccination against infection.