Immunogenicity of Whole-Parasite Vaccines against Plasmodium falciparum Involves Malarial Hemozoin and Host TLR9

被引：120

作者：

Coban, Cevayir ^{[1
]}

Igari, Yoshikatsu ^{[1
,6
]}

Yagi, Masanori ^{[2
]}

Reimer, Thornik ^{[4
,5
]}

Koyama, Shohei ^{[1
]}

Aoshi, Taiki ^{[2
]}

Ohata, Keiichi ^{[1
,6
]}

Tsukui, Toshihiro ^{[6
]}

Takeshita, Fumihiko ^{[7
]}

Sakurai, Kazuo ^{[8
]}

Ikegami, Takahisa ^{[3
]}

Nakagawa, Atsushi ^{[3
]}

Horii, Toshihiro ^{[2
]}

Nunez, Gabriel ^{[4
,5
]}

Ishii, Ken J. ^{[1
,2
]}

Akira, Shizuo ^{[1
]}

机构：

[1] Osaka Univ, Host Def Lab, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Microbial Dis Res Inst, Dept Mol Protozool, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan

[4] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Ctr Comprehens Canc, Sch Med, Ann Arbor, MI 48109 USA

[6] Nippon Zenyaku Kogyo Co Ltd, ZENOAQ, Fukushima 9630196, Japan

[7] Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Yokohama, Kanagawa 2360004, Japan

[8] Univ Kitakyushu, Dept Chem Proc & Environm, Fukuoka 8080135, Japan

来源：

CELL HOST & MICROBE | 2010年 / 7卷 / 01期

基金：

美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

MURINE CEREBRAL MALARIA; INNATE IMMUNE-RESPONSE; PIGMENT BETA-HEMATIN; TOLL-LIKE RECEPTOR-9; NALP3; INFLAMMASOME; CYTOPLASMIC DNA; CELL; ACTIVATE; TOLL-LIKE-RECEPTOR-9; RECOGNITION;

D O I：

10.1016/j.chom.2009.12.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：50 / 61

页数：12

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