| Literature DB >> 20114028 |
Cevayir Coban1, 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 Nuñez, Ken J Ishii, Shizuo Akira.
Abstract
Although 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. 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20114028 DOI： 10.1016/j.chom.2009.12.003
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023