Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant
Hemozoin (Hz) is a heme crystal produced during malaria infection that stimulates immune cells, leading to the production of cytokines and chemokines. The immunostimulatory action of Hz has previously been applied in the development of alternative adjuvants. Crystallization of hemin is a chemical approach for producing Hz. Here, we focused on an enzymatic production method for Hz using the heme detoxification protein (HDP), which catalyzes heme dimer formation from hemin in <i>Plasmodium</i>. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant <i>Plasmodium falciparum</i> HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading to the production of interleukin (IL)-6 and IL-12p40. In mice, subcutaneous administration of esHz together with an antigen, ovalbumin (OVA), increased the OVA-specific immunoglobulin (Ig) G2c isotype level in the serum, whereas OVA-specific IgG1 was not induced. Our findings suggest that esHz is a useful Th-1 cell adjuvant.
Authors
- Wakako Tsugawa (ORCID: https://orcid.org/0000-0001-6299-5267)
- Anh Thi Tram Tu (ORCID: https://orcid.org/0000-0002-7243-2086)
- Kazuaki Hoshi
- Koji Sode (ORCID: https://orcid.org/0000-0002-9833-2091)
- Leif Bülow (ORCID: https://orcid.org/0000-0003-4966-8610)
- Miwako Shobo (ORCID: https://orcid.org/0009-0009-1771-8004)
- Ryutaro Asano (ORCID: https://orcid.org/0000-0001-6795-8377)
- Tetsuya Furuya (ORCID: https://orcid.org/0000-0003-3979-7072)
- Lei Ye (ORCID: https://orcid.org/0000-0002-3646-4072)
- Yoji Hakamata (ORCID: https://orcid.org/0000-0002-0138-6692)
- Karin Kettisen (ORCID: https://orcid.org/0000-0002-2985-0944)
- Kazunori Ikebukuro (ORCID: https://orcid.org/0000-0003-2838-0562)
- Tomohiko Yamazaki (ORCID: https://orcid.org/0000-0003-2136-8042)
Institutions
- University of North Carolina at Chapel Hill (US)
- Vietnam National University Ho Chi Minh City (VN)
- Nippon Veterinary and Life Science University (JP)
- North Carolina State University (US)
- Lund University (SE)
- Hokkaido University (JP)
- National Institute for Materials Science (JP)
- Ho Chi Minh City University of Science (VN)
- Tokyo University of Agriculture and Technology (JP)
Publication Details
- Journal
- Nanomaterials
- Published
- 2024-09-03
- DOI
- https://doi.org/10.3390/nano14171440
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- National Institute for Materials Science