Myeloid cells are necessary for the host control of a (burden and limit disease progression by activating pro-inflammatory signaling pathways, recruiting additional phagocytes, ingesting bacilli, up-regulating bactericidal mechanisms and inducing antigen-specific adaptive immunity (7C9). and proliferation of helper and cytotoxic T-cells (15, 16). T-cell immunosuppression was attributed to the presence of macrophage-like natural suppressor cells, the production of high levels of IL-1 and soluble suppressive factors (16, 19). Natural suppressor cells were later linked to MDSC. Natural suppressor cells from mice exposed to mycobacterial products in Complete Freud’s adjuvant (CFA), shared comparable phenotypic and functional features with MDSC (10). These cells highly expressed the NKP-1339 markers of ITGA9 myeloid origin and differentiation, Gr-1 and CD11b, and inhibition of T-cell proliferation and IFN- production was linked to NO production in splenocytes (10). Subsequent studies validated the presence of MDSC during BCG contamination (13) and in patients with active TB (14). Thus, initial observations of natural suppressor cells were during mycobacterial insult and established that this generation of these cells was driven by the mycobacterial products. MDSC Characterization in Mycobacterial Infections Identification of MDSC requires a combination of assays comprising of immunophenotyping, enzyme measurements, and suppressive assessments (20). Markers employed NKP-1339 for detection of human MDSC allow, to some extent, their differentiation from monocytes and neutrophils, although this is cumbersome in mice (21). At present, three commonly reported MDSC subsets identified in human TB include early stage MDSC (e-MDSC), polymorphonuclear-MDSC (PMN-MDSC), and monocytic-MDSC (M-MDSC) (14, 22, 23). Immunosuppressive eosinophilic MDSC have recently been described during chronic contamination but require validation in other diseases (24). MDSC enriched in TB patients, according to recent recommendations using a ficoll density-gradient (22, 23), have been classified as e-MDSC (LIN1?HLA-DR?/loCD11b+CD33+), PMN-MDSC (HLA-DR?/loCD11b+CD14?Compact disc15+Compact disc33+/dim) and M-MDSC (HLA-DR?/lowCD11b+CD14+CD15?Compact disc33+) (20). Of a particular subset Rather, M-MDSC inhabitants has been referred to as a heterogenous inhabitants of cells, in various maturation levels (20). Since you can find no particular markers for MDSC, ambiguity with various other myeloid cells which have equivalent phenotypic features and useful properties exists, especially after pathogen exposure. For instance, contamination of monocytes with fungal cells and exposure to fungal components subverts monocyte differentiation to immunosuppressive dendritic cells. The phenotype of the subverted DC is usually characterized by the expression of CD14 with a lack of CD1a molecule, presence of CD83 and CD86 but a relatively low expression of MHC class II and CD80. These cells produce IL-12 but are associated with the release of IL-10 and IL-6 (25). Similarly our group has exhibited that CD14+ M-MDSC production of IL-10 and IL-6 is usually associated with either absent, or relatively low levels of NKP-1339 HLA-DR NKP-1339 and CD80 (14, 26). Thus, an unequivocal marker that is able to distinguish myeloid cell populace and subsets in biological NKP-1339 samples such as whole blood culture and tissue is required. Whilst there is no specific marker for M-MDSC yet, utilization of LOX-1 as a unique PMN-MDSC marker has been proposed but (27) requires validation in TB patients. In murine TB, PMN-MDSC are phenotypically Gr-1+CD11b+Ly6G+Ly6Clo/int and M-MDSC Gr-1+CD11b+Ly6G?/l0Ly6Chi, yet functional assays are essential for their classification (28C30). Morphological characterization has been used as a confirmatory tool to distinguish MDSC from other myeloid cells in TB samples (22, 28). Immature myeloid cells identified as PMN-MDSC share comparable morphological characteristics with neutrophils, as they show ring-shaped or band nuclei. This nuclear shape can, however, be present in neutrophil progenitors and young neutrophils. Utilization of CD10 for human specimens (21) along with suppressive assays may help distinguish PMN-MDSC from non-suppressive immature neutrophils. MDSC likely encompass cells at different maturation stages with a distinct activation status and functional role. For instance, growth of MDSC with the phenotype Lin?/l0HLA-DR?/loCD11b+CD14+CD33+Compact disc80+, was described.