The induction of innate and adaptive immunity by biodegradable poly(γ-glutamic acid) nanoparticles via a TLR4 and MyD88 signaling pathway

被引：122

作者：

Uto, Tomofumi ^{[1
,4
]}

Akagi, Takami ^{[2
,4
]}

Yoshinaga, Keisuke ^{[3
,4
]}

Toyama, Masaaki ^{[1
]}

Akashi, Mitsuru ^{[2
,4
]}

Baba, Masanori ^{[1
,4
]}

机构：

[1] Kagoshima Univ, Grad Sch Med & Dent Sci, Div Antiviral Chemotherapy, Ctr Chron Viral Dis, Kagoshima 8908544, Japan

[2] Osaka Univ, Grad Sch Engn, Dept Appl Chem, Suita, Osaka 5650871, Japan

[3] Kumamoto Natl Coll Technol, Dept Biol & Chem Syst Engn, Yatsushiro 8668501, Japan

[4] Japan Sci & Technol Agcy JST, Core Res Evolut Sci & Technol CREST, Tokyo 1500002, Japan

来源：

BIOMATERIALS | 2011年 / 32卷 / 22期

基金：

日本科学技术振兴机构;

关键词：

Nanoparticle; Adjuvant; Antigen carrier; Toll-like receptor; TOLL-LIKE RECEPTORS; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; DENDRITIC CELLS; VACCINE ADJUVANTS; ACTIVATION; RECOGNITION; PROTEIN; DELIVERY; GP120;

D O I：

10.1016/j.biomaterials.2011.03.052

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

The induction of adaptive immunity through the activation of innate immunity is indispensable for vaccine development. Although strategies for particulate antigen delivery are widely investigated, their immunological mechanisms are unclear. We describe in this study that biodegradable nanoparticles (NPs) elaborated with poly(gamma-glutamic acid) (gamma-PGA) are able to induce potent innate and adaptive immune responses through Toll-like receptor 4 (TLR4) and MyD88 signaling pathways. The production of inflammatory cytokines from macrophages and the maturation of dendritic cells were impaired in MyD88-knockout and TLR4-deficient mice compared with their wild-types, when the cells were stimulated with gamma-PGA NPs. The immunization of these mice with antigen-carrying gamma-PGA NPs also resulted in diminished induction of antigen-specific cellular immune responses. These results suggest that gamma-PGA NPs have not only an antigen-carrying capacity but also a potent adjuvant function of eliciting adaptive immune responses to the carrying antigen through recognition of the first-line host-sensor system. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：5206 / 5212

页数：7

共 30 条

[1] Preparation and characterization of biodegradable nanoparticles based on poly(γ-glutamic acid) with L-phenylalanine as a protein carrier [J].