Induction of Protective Immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina Infections Using Dendritic Cell-Derived Exosomes
Induction of Protective Immunity against Eimeria tenella, Eimeria maxima, and Eimeria acervulina Infections Using Dendritic Cell-Derived Exosomes
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DOI：
10.1128/iai.06413-11
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发表时间：
2012-05-01
影响因子：
3.1
通讯作者：
Sanchez-Acedo, Caridad
中科院分区：
文献类型：
--
作者：
del Cacho, Emilio;Gallego, Margarita;Sanchez-Acedo, Caridad
本研究描述了一种利用载有艾美耳虫抗原（Ag）的树突状细胞（dc）衍生的外体对抗禽球虫病的新免疫策略。用从柔嫩艾美耳球虫、maxima艾美耳球虫和acervulina艾美耳球虫中提取的Ags混合液分离鸡肠道dc，并分离细胞来源的外泌体。用外泌体对鸡进行不免疫或肌内免疫，随后不感染或同时感染柔嫩肠杆菌、大肠杆菌和棘皮肠杆菌卵囊。比较未免疫/未感染组、未免疫/感染组和免疫/感染组的免疫参数是分泌T(h)1细胞因子、T(h)2细胞因子、白细胞介素-16 （IL-16）和ag反应性抗体的细胞数量，这些细胞在体外和体内对艾美耳球虫感染的保护性免疫数据。免疫和感染鸡的盲肠扁桃体、Peyer's斑块和脾脏分泌IL-16和T(h)1细胞因子IL-2和γ干扰素的细胞数量增加，ag刺激的增殖反应更大，与未免疫/未感染和未免疫/感染对照相比，孢子子Ags体外刺激后，ag反应性IgG和iga产生细胞数量增加。与未免疫/未感染和未免疫/感染对照相比，免疫组和感染组分泌T(h)2细胞因子IL-4和IL-10的细胞数量减少。用载银外泌体免疫并在体内感染艾美耳球虫卵囊的鸡，与未免疫/感染的对照组相比，体重增加增加，饲料转化率降低，粪便卵囊脱落减少，肠道病变评分减轻，死亡率降低。这些结果表明，利用从艾美耳球虫中分离的抗原孵育的dc衍生的外泌体成功地进行禽球虫病的现场疫苗接种是可能的。
This study describes a novel immunization strategy against avian coccidiosis using exosomes derived from Eimeria parasite antigen (Ag)-loaded dendritic cells (DCs). Chicken intestinal DCs were isolated and pulsed in vitro with a mixture of sporozoite-extracted Ags from Eimeria tenella, E. maxima, and E. acervulina, and the cell-derived exosomes were isolated. Chickens were nonimmunized or immunized intramuscularly with exosomes and subsequently noninfected or coinfected with E. tenella, E. maxima, and E. acervulina oocysts. Immune parameters compared among the nonimmunized/noninfected, nonimmunized/infected, and immunized/infected groups were the numbers of cells secreting T(h)1 cytokines, T(h)2 cytokines, interleukin-16 (IL-16), and Ag-reactive antibodies in vitro and in vivo readouts of protective immunity against Eimeria infection. Cecal tonsils, Peyer's patches, and spleens of immunized and infected chickens had increased numbers of cells secreting the IL-16 and the T(h)1 cytokines IL-2 and gamma interferon, greater Ag-stimulated proliferative responses, and higher numbers of Ag-reactive IgG- and IgA-producing cells following in vitro stimulation with the sporozoite Ags compared with the nonimmunized/noninfected and nonimmunized/infected controls. In contrast, the numbers of cells secreting the T(h)2 cytokines IL-4 and IL-10 were diminished in immunized and infected chickens compared with the nonimmunized/noninfected and the nonimmunized/infected controls. Chickens immunized with Ag-loaded exosomes and infected in vivo with Eimeria oocysts had increased body weight gains, reduced feed conversion ratios, diminished fecal oocyst shedding, lessened intestinal lesion scores, and reduced mortality compared with the nonimmunized/infected controls. These results suggest that successful field vaccination against avian coccidiosis using exosomes derived from DCs incubated with Ags isolated from Eimeria species may be possible.