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Role of the mannose receptor (CD206) in innate immunity to ricin toxin

Emily Gage1, Maria O Hernandez, Joanne M O'Hara

  • 1Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA. gage.emily@gmail.com

Toxins
|November 10, 2011
PubMed

Insights

The mannose receptor (MR) facilitates ricin toxin uptake in monocytes. However, MR knockout mice showed increased susceptibility to ricin, suggesting MR protects against ricin toxicity in vivo.

Area of Science:

  • Immunology
  • Toxicology
  • Cell Biology

Background:

  • Ricin toxin causes inflammation and organ failure.
  • The mannose receptor (MR; CD206) is hypothesized to facilitate ricin uptake into macrophages.
  • MR recognizes oligosaccharide side chains on ricin's A (RTA) and B (RTB) subunits.

Purpose of the Study:

  • To investigate the role of the mannose receptor (MR) in ricin toxin pathogenesis.
  • To determine if MR facilitates ricin binding, uptake, and toxicity in vivo.

Main Methods:

  • In vitro experiments confirmed MR promotes ricin binding, uptake, and monocyte killing.
  • In vivo studies utilized MR knockout (MR(-/-)) mice challenged with ricin.
  • Mice were administered varying doses of ricin via intraperitoneal injection.

Main Results:

  • MR knockout mice exhibited significantly higher susceptibility to ricin-induced death compared to wild-type controls.
  • In vitro data confirmed MR's role in ricin uptake and toxicity.
  • In vivo results contradicted the hypothesis of MR facilitating ricin toxicity.

Conclusions:

  • The mannose receptor (MR) plays a protective role against ricin toxicity in vivo.
  • MR likely functions in scavenging and degrading ricin, rather than facilitating its uptake and toxicity.
  • These findings challenge the proposed mechanism of MR-mediated ricin pathogenesis.
Keywords:
C-type lectinsbiodefensepathogenesistoxin

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