Role of myeloid-derived suppressor cells and regulatory t-cells in the tuberculous granuloma

Abstract

In the course of Mycobacterium tuberculosis (M. tb) infection, while a robust immune response is required for containment and clearance of the pathogen, immune-mediated tissue damage may also occur. Immune suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are recruited to the site of infection, but in the process of controlling immune responses can promote pathogen survival. Tregs are known to be elevated in tuberculosis (TB) patients with active disease and studies in animal models demonstrate that Tregs inhibit effector T cell function through multiple mechanisms during M. tb infection (Guyot-Revol et al., Am J Respir Crit Care Med 173:803-10, 2006). More recently, increased levels of MDSCs have been found in patients with active TB and although less is known about their role in infection, it has become clear that MDSCs are very effective in suppressing T cell responses in tumors (El Daker et al., PLoS One 10:e0123772, 2015). In this chapter, we will give a brief overview of the early immune response to M. tb. infection and the host's attempt to contain infection through the formation of granulomas in the lung. We will then review the function of MDSCs and Tregs and what is known about their role during TB infection. Finally, we will discuss currently available drugs that can target these cell populations and their potential use for the treatment of TB.