Role of the Mannose Receptor (CD206) in Innate Immunity to Ricin Toxin

Abstract

The entry of ricin toxin into macrophages and certain other cell types in the spleen and liver results in toxin-induced inflammation, tissue damage and organ failure. It has been proposed that uptake of ricin into macrophages is facilitated by the mannose receptor (MR; CD206), a C-type lectin known to recognize the oligosaccharide side chains on ricin’s A (RTA) and B (RTB) subunits. In this study, we confirmed that the MR does indeed promote ricin binding, uptake and killing of monocytes in vitro. To assess the role of MR in the pathogenesis of ricin in vivo, MR knockout (MR−/−) mice were challenged with the equivalent of 2.5× or 5× LD50 of ricin by intraperitoneal injection. We found that MR−/− mice were significantly more susceptible to toxin-induced death than their age-matched, wild-type control counterparts. These data are consistent with a role for the MR in scavenging and degradation of ricin, not facilitating its uptake and toxicity in vivo.

Immunity to Ricin: Fundamental Insights into Toxin–Antibody Interactions

“…While these studies support a role of the MR in promoting toxicity of ricin in vivo, recent results from ricin challenge studies of MR deficient mice revealed the opposite outcome. MR knockout mice proved to be more sensitive to ricin-induced death than their wild-type counterparts, which is consistent with a role for the MR in clearance and degradation of ricin toxin, and not enhancement of toxin uptake (Gage et al 2011). The MR will not be discussed further in this chapter.…”

Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation

“…Mannosylated-mediated processing is commonly associated with endocytic trafficking towards recycling mechanisms (to refresh surface CD206)[42] and through proposed additional endocytic vesicles (early to late endosome)[43]. Whereas, other studies have indicated that general phagocytosis does not contribute significantly to biomolecule release, representing less than 5% of processed cargo[44]. Thus, mannosylation of PBAEs is clearly triggering uptake and processing mechanisms beneficial to eventual gene delivery.…”

Role of Endothelial N-Glycan Mannose Residues in Monocyte Recruitment During Atherogenesis

“…MR receptor is expressed on a variety of monocyte derived cell populations including alternatively activated M2 macrophages and dendritic cells 49 . There is also evidence that MR is present on monocytes as ricin toxin induced apoptosis of THP-1 monocytes can be attenuated with anti-MR antibodies 50 . Lesion localized MR expressing macrophages do not associate with lipids and do not transition into foam cells 51 , suggesting they are serving a non-traditional function within the plaques, possibly recruited to the region by the mannose residues on the luminal surface.…”