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The C-type Lectin Receptor CLEC12A Recognizes Plasmodial Hemozoin and Contributes to Cerebral Malaria Development

Marie-Kristin Raulf1, Timo Johannssen2, Svea Matthiesen3

  • 1Immunology Unit and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Lower Saxony, Germany; Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, 30559 Hannover, Lower Saxony, Germany.

Cell Reports
|July 4, 2019
PubMed

Insights

Researchers identified C-type lectin receptor CLEC12A as a sensor for hemozoin, a malaria toxin. CLEC12A deficiency protects against experimental cerebral malaria, offering new insights into innate immunity and malaria pathogenesis.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Cell Biology

Background:

  • Malaria is a significant infectious disease mortality cause.
  • Hemozoin, a Plasmodium byproduct, exacerbates cerebral malaria.
  • The innate immune recognition of hemozoin remains poorly understood.

Purpose of the Study:

  • To identify the specific C-type lectin receptor (CLR) responsible for hemozoin recognition.
  • To investigate the role of this CLR in T cell activation and experimental cerebral malaria (ECM).

Main Methods:

  • Utilized dendritic cell-T cell co-culture assays.
  • Employed the Plasmodium berghei Antwerpen-Kasapa (ANKA) mouse model for experimental cerebral malaria.
  • Assessed the impact of CLEC12A deficiency on immune responses and disease progression.

Main Results:

  • Identified CLEC12A as a direct receptor for hemozoin.
  • Demonstrated that CLEC12A/hemozoin interaction enhances CD8+ T cell cross-priming.
  • Showed that CLEC12A-deficient mice are protected from ECM, exhibiting reduced incidence and milder symptoms.

Conclusions:

  • CLEC12A functions as an innate immune sensor for Plasmodium-derived hemozoin.
  • Targeting the CLEC12A pathway may offer a novel therapeutic strategy for cerebral malaria.
Keywords:
C-type lectin receptorMICL/CLEC12APlasmodium bergheicerebral malariahemozoin

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