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Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant

Hoshi, Kazuaki ; Tu, Anh Thi Tram ; Shobo, Miwako ; Kettisen, Karin LU ; Ye, Lei LU orcid ; Bülow, Leif LU ; Hakamata, Yoji ; Furuya, Tetsuya ; Asano, Ryutaro and Tsugawa, Wakako , et al. (2024) In Nanomaterials 14(17).
Abstract

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 Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading... (More)

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 Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adjuvant, heme detoxification protein, hemozoin analog, Th-1 immunity, vaccine
in
Nanomaterials
volume
14
issue
17
article number
1440
publisher
MDPI AG
external identifiers
  • pmid:39269102
  • scopus:85203680041
ISSN
2079-4991
DOI
10.3390/nano14171440
language
English
LU publication?
yes
id
5f6022c8-f7ee-4049-bbfe-1b5c60f20b9f
date added to LUP
2024-11-15 10:58:11
date last changed
2025-07-12 07:19:50
@article{5f6022c8-f7ee-4049-bbfe-1b5c60f20b9f,
  abstract     = {{<p>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 Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum 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.</p>}},
  author       = {{Hoshi, Kazuaki and Tu, Anh Thi Tram and Shobo, Miwako and Kettisen, Karin and Ye, Lei and Bülow, Leif and Hakamata, Yoji and Furuya, Tetsuya and Asano, Ryutaro and Tsugawa, Wakako and Ikebukuro, Kazunori and Sode, Koji and Yamazaki, Tomohiko}},
  issn         = {{2079-4991}},
  keywords     = {{adjuvant; heme detoxification protein; hemozoin analog; Th-1 immunity; vaccine}},
  language     = {{eng}},
  number       = {{17}},
  publisher    = {{MDPI AG}},
  series       = {{Nanomaterials}},
  title        = {{Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant}},
  url          = {{http://dx.doi.org/10.3390/nano14171440}},
  doi          = {{10.3390/nano14171440}},
  volume       = {{14}},
  year         = {{2024}},
}