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Get Free AccessAlthough whole-parasite vaccine strategies for malaria infection have regained attention, their immunological mechanisms of action remain unclear. We find that immunization of mice with a crude blood stage extract of the malaria parasite Plasmodium falciparum elicits parasite antigen-specific immune responses via Toll-like receptor (TLR) 9 and that the malarial heme-detoxification byproduct, hemozoin (HZ), but not malarial DNA, produces a potent adjuvant effect. Malarial and synthetic (s)HZ bound TLR9 directly to induce conformational changes in the receptor. The adjuvant effect of sHZ depended on its method of synthesis and particle size. Although natural HZ acts as a TLR9 ligand, the adjuvant effects of synthetic HZ are independent of TLR9 or the NLRP3-inflammasome but are dependent on MyD88. The adjuvant function of sHZ was further validated in a canine antiallergen vaccine model. Thus, HZ can influence adaptive immune responses to malaria infection and may have therapeutic value in vaccine adjuvant development.
Cevayir Coban, Yoshikatsu Igari, Masanori Yagi, Thornik Reimer, Shohei Koyama, Taiki Aoshi, Keiichi Ohata, Toshihiro Tsukui, Fumihiko Takeshita, Kazuo Sakurai, Takahisa Ikegami, Atsushi Nakagawa, Toshihiro Horii, Gabriel Núñez, Ken J. Ishii, Akira Shizuo (2010). Immunogenicity of Whole-Parasite Vaccines against Plasmodium falciparum Involves Malarial Hemozoin and Host TLR9. Cell Host & Microbe, 7(1), pp. 50-61, DOI: 10.1016/j.chom.2009.12.003.
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Type
Article
Year
2010
Authors
16
Datasets
0
Total Files
0
Language
English
Journal
Cell Host & Microbe
DOI
10.1016/j.chom.2009.12.003
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