Exploitation of the Macrophage Mannose Receptor (CD206) in Infectious Disease Diagnostics and Therapeutics

Abstract

The macrophage mannose receptor (MR, CD206) is a C-type lectin expressed predominantly by most tissue macrophages, dendritic cells and specific lymphatic or endothelial cells. It functions in endocytosis and phagocytosis, and plays an important role in immune homeostasis by scavenging unwanted mannoglycoproteins. More attention is being paid to its particularly high expression in tissue pathology sites during disease such the tumor microenvironment. The MR recognizes a variety of microorganisms by their mannan-coated cell wall, which is exploited by adapted intracellular pathogens such as Mycobacterium tuberculosis, for their own survival. Despite the continued development of drug delivery technologies, the targeting of agents to immune cells, especially macrophages, for effective diagnosis and treatment of chronic infectious diseases has not been addressed adequately. In this regard, strategies that optimize MR-mediated uptake by macrophages in target tissues during infection are becoming an attractive approach. We review important progress in this area.

Figure 1

Schematic diagram for the roles of the macrophage mannose receptor (MR, CD206) in pathogen recognition [e.g., Mycobacterium tuberculosis (M.tb)]; and in specific binding of mannosylated liposomes, siRNAs, various drug molecules, and radioisotopes like ⁹⁹Tc as well as MR-nanobodies.

Figure 2

Schematic diagram of the granuloma microenvironment to illustrate the cellular architecture of a typical tuberculosis (TB) granuloma, where M.tb is contained by various immune cells including macrophages and foamy cells, which are predicted to express abundant levels of the MR. Neutrophils may also be present when there is a large amount of necrosis and tissue destruction. Since the MR is a rapidly recycling receptor, mannosylated imaging, diagnostic and chemotherapeutic agents efficiently bound to the MR are delivered to and accumulate in receptor-containing cells of the target tissues.