Synthetic hemozoin as a nanocarrier for cross-presentation

Conventional antigen presentation is known to involve phagocytosis of antigens followed by their internalization into endocytic compartments and epitope presentation via MHC class II molecules to CD4 T cells. However, since 1976, a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in cross-presentation, the Dectin-1 cluster C-type lectin receptor (CLECs), particularly the CLEC9A receptor, is not only expressed on dendritic cells but also plays a key role in this context. In particular, CLEC12A has been highlighted as a receptor for the malaria pigment hemozoin (HZ). During Plasmodium infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow the coupling of the substance followed by its coating. First, it was found that sHz can transport coated and coupled antigens, the compounds can associate with LAMP1-positive vesicles and decrease the overall intracellular pH, which can potentially increase the cross-presentation of ovalbumin and Leishmania infantum antigens. Thus, this study adds important insights into the molecular complexities of antigen presentation, showing not only the immunomodulatory properties of sHz, but also its potential applications as an antigen carrier.

Project details

Basic Science
Immunology

Nov 2024 — Apr 2025

Brazil