Humanized HLA-DR4 mice fed with the protozoan pathogen of oysters Perkinsus marinus (Dermo) do not develop noticeable pathology but elicit systemic immunity.
Humanized HLA-DR4 mice fed with the protozoan pathogen of oysters Perkinsus marinus (Dermo) do not develop noticeable pathology but elicit systemic immunity.
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DOI：
10.1371/journal.pone.0087435
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Casares S
中科院分区：
文献类型：
--
作者：
Wijayalath W;Majji S;Kleschenko Y;Pow-Sang L;Brumeanu TD;Villasante EF;Vasta GR;Fernández-Robledo JA;Casares S
海洋帕金虫（Perkinsus marinus）是一种寄生于海洋的原生动物，可引起牡蛎的“皮肤病”，对贝类养殖业和河口环境造成严重危害。据估计，在某些地区，感染率高达100%，通常会导致感染后1-2年内死亡。因此，人类可能会通过受感染的牡蛎食用寄生虫，但据我们所知，尚未在人类或其他哺乳动物中研究过口服食用P. marinus的影响。为了解决这个问题，我们使用了表达HLA-DR 4分子并且缺乏小鼠MHC-II类分子（DR4.EA0）表达的人源化小鼠，使得CD 4 T细胞应答仅受人HLA-DR 4分子限制。DR4.EA0小鼠在单次或重复喂食活的海洋毕赤酵母寄生虫后，未发生腹泻或胃肠道或肺中任何可检测到的病理学。此外，肠道相关淋巴组织和脾脏中的淋巴细胞群在寄生虫喂养的小鼠中未发生改变，排除了局部或全身炎症。值得注意的是，未经处理的DR4.EA0小鼠具有针对海洋疟原虫寄生虫的抗体（IgM和IgG），而寄生虫特异性T细胞应答是不可检测的。投喂海拟单胞菌可增强抗体应答，并刺激针对牡蛎寄生虫的特异性细胞免疫（IFNγ）。我们的数据表明，海疟原虫寄生虫能够诱导DR4.EA0小鼠的全身免疫力，而不会引起明显的病理学，并支持使用基因工程改造的海疟原虫作为新的口服疫苗平台来诱导针对感染因子的全身免疫力的基本原理。
Perkinsus marinus (Phylum Perkinsozoa) is a marine protozoan parasite responsible for “Dermo” disease in oysters, which has caused extensive damage to the shellfish industry and estuarine environment. The infection prevalence has been estimated in some areas to be as high as 100%, often causing death of infected oysters within 1–2 years post-infection. Human consumption of the parasites via infected oysters is thus likely to occur, but to our knowledge the effect of oral consumption of P. marinus has not been investigated in humans or other mammals. To address the question we used humanized mice expressing HLA-DR4 molecules and lacking expression of mouse MHC-class II molecules (DR4.EA0) in such a way that CD4 T cell responses are solely restricted by the human HLA-DR4 molecule. The DR4.EA0 mice did not develop diarrhea or any detectable pathology in the gastrointestinal tract or lungs following single or repeated feedings with live P. marinus parasites. Furthermore, lymphocyte populations in the gut associated lymphoid tissue and spleen were unaltered in the parasite-fed mice ruling out local or systemic inflammation. Notably, naïve DR4.EA0 mice had antibodies (IgM and IgG) reacting against P. marinus parasites whereas parasite specific T cell responses were undetectable. Feeding with P. marinus boosted the antibody responses and stimulated specific cellular (IFNγ) immunity to the oyster parasite. Our data indicate the ability of P. marinus parasites to induce systemic immunity in DR4.EA0 mice without causing noticeable pathology, and support rationale grounds for using genetically engineered P. marinus as a new oral vaccine platform to induce systemic immunity against infectious agents.
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影响因子：
9.6
作者：
Fernandez-Robledo, Jose A.;Vasta, Gerardo R.
通讯作者：
Vasta, Gerardo R.
DOI：
10.1084/jem.183.6.2635
发表时间：
1996-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ito K;Bian HJ;Molina M;Han J;Magram J;Saar E;Belunis C;Bolin DR;Arceo R;Campbell R;Falcioni F;Vidović D;Hammer J;Nagy ZA
通讯作者：
Nagy ZA
影响因子：
3.4
作者：
GAUTHIER, JD;VASTA, GR
通讯作者：
VASTA, GR
影响因子：
3.5
作者：
Khansa, Sara;Hoteit, Rouba;Mahfouz, Rami A. R.
通讯作者：
Mahfouz, Rami A. R.
影响因子：
6.7
作者：
Hird TR;Grassly NC
通讯作者：
Grassly NC