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

Cell Rep. 2019 Jul 2;28(1):30-38.e5. doi: 10.1016/j.celrep.2019.06.015.

Abstract

Malaria represents a major cause of death from infectious disease. Hemozoin is a Plasmodium-derived product that contributes to progression of cerebral malaria. However, there is a gap of knowledge regarding how hemozoin is recognized by innate immunity. Myeloid C-type lectin receptors (CLRs) encompass a family of carbohydrate-binding receptors that act as pattern recognition receptors in innate immunity. In the present study, we identify the CLR CLEC12A as a receptor for hemozoin. Dendritic cell-T cell co-culture assays indicate that the CLEC12A/hemozoin interaction enhances CD8+ T cell cross-priming. Using the Plasmodium berghei Antwerpen-Kasapa (ANKA) mouse model of experimental cerebral malaria (ECM), we find that CLEC12A deficiency protects mice from ECM, illustrated by reduced ECM incidence and ameliorated clinical symptoms. In conclusion, we identify CLEC12A as an innate sensor of plasmodial hemozoin.

Keywords: C-type lectin receptor; MICL/CLEC12A; Plasmodium berghei; cerebral malaria; hemozoin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cross-Priming
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Granzymes / metabolism
  • Hemeproteins / immunology*
  • Immunity, Innate
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Malaria, Cerebral / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium berghei / pathogenicity*
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / immunology*
  • T-Lymphocytes

Substances

  • CLEC12A protein, human
  • CLEC12A protein, mouse
  • Hemeproteins
  • Lectins, C-Type
  • Receptors, Mitogen
  • hemozoin
  • Granzymes