The Emerging Role of Myeloid-Derived Suppressor Cells in Tuberculosis

Abstract

Myeloid cells are crucial for the host control of a Mycobacterium tuberculosis (M.tb) infection, however the adverse role of specific myeloid subsets has increasingly been appreciated. The relevance of such cells in therapeutic strategies and predictive/prognostic algorithms is to promote interest in regulatory myeloid cells in tuberculosis (TB). Myeloid-derived suppressor cells (MDSC) are a heterogeneous collection of phagocytes comprised of monocytic- and polymorphonuclear cells that exhibit a potent suppression of innate- and adaptive immune responses. Accumulation of MDSC under pathological conditions associated with chronic inflammation, most notably cancer, has been well-described. Evidence supporting the involvement of MDSC in TB is increasing, yet their significance in this infection continues to be viewed with skepticism, primarily due to their complex nature and the lack of genetic evidence unequivocally discriminating these cells from other terminally differentiated myeloid populations. Here we highlight recent advances in MDSC characterization and summarize findings on the TB-induced hematopoietic shift associated with MDSC expansion. Lastly, the mechanisms of MDSC-mediated disease progression and future research avenues in the context of TB therapy and prophylaxis are discussed.

Keywords: Mycobacterium tuberculosis; immunosuppression; infectious disease; innate immunity; myeloid-derived suppressor cells.

Figure 1

(A) Mediators of MDSC expansion and activation in a mycobacterial environment. A schematic depicting mediators associated with the proposed “two-signal” MDSC expansion and activation process, in a mycobacterial environment. These include cytokines, chemokines, calcium-binding proteins, and matrix metalloproteinases. (B) MDSC cellular interaction and mediators of immunosuppression in a mycobacterial environment. Examples of the known and suggested interactions of MDSC with other immune cells in the mycobacterial setting, including the soluble mediators associated with their immunosuppressive activity.