Sublingual Vaccine with GroEL Attenuates Atherosclerosis
Sublingual Vaccine with GroEL Attenuates Atherosclerosis
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DOI：
10.1177/0022034514523784
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发表时间：
2014-04-01
影响因子：
7.6
通讯作者：
Yamamoto, M.
中科院分区：
文献类型：
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作者：
Hagiwara, M.;Kurita-Ochiai, T.;Yamamoto, M.
热休克蛋白60（HSP 60）的自身免疫反应有助于动脉粥样硬化的进展，而HSP 60的免疫可能会诱导动脉粥样硬化保护反应。我们评估了针对牙龈卟啉单胞菌（rGroEL）的重组HSP 60的抗动脉粥样硬化疫苗诱导保护性粘膜免疫应答的能力。雌性载脂蛋白E缺陷型自发性高脂血症（Apoe（shl））小鼠在牙龈卟啉单胞菌381注射之前接受rGroEL的舌下递送。16周后对动物实施安乐死。用rGroEL的舌下免疫诱导显著的rGroEL特异性血清IgG应答。从脾分离的抗原特异性细胞在体外抗原再刺激后产生显著高水平的IL-10和IFN-γ。流式细胞术分析显示，IL-10（+）和IFN-γ（+）CD 4（+）Foxp 3（+）细胞在下颌下腺（SMG）中的频率均显著增加。此外，舌下免疫rGroEL显着减少动脉粥样硬化病变形成的主动脉窦和降低血清CRP，MCP-1和ox-LDL水平。这些发现表明，舌下免疫rGroEL与SMG中IFN γ（+）或IL-10（+）Foxp 3（+）细胞的增加和全身体液应答相关，这可能是预防自然发生或牙龈卟啉单胞菌加速的动脉粥样硬化的有效策略。
Autoimmune responses to heat-shock protein 60 (HSP60) contribute to the progression of atherosclerosis, whereas immunization with HSP60 may induce atheroprotective responses. We assessed the capacity of an atheroprotective vaccine that targeted a recombinant HSP60 from Porphyromonas gingivalis (rGroEL) to induce a protective mucosal immune response. Female apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice received sublingual delivery of rGroEL prior to P. gingivalis 381 injection. The animals were euthanized 16 weeks later. Sublingual immunization with rGroEL induced significant rGroEL-specific serum IgG responses. Antigen-specific cells isolated from spleen produced significantly high levels of IL-10 and IFN-gamma after antigen re-stimulation in vitro. Flow cytometric analysis indicated that the frequencies of both IL-10(+) and IFN-gamma(+) CD4(+) Foxp3(+) cells increased significantly in submandibular glands (SMG). Furthermore, sublingual immunization with rGroEL significantly reduced atherosclerosis lesion formation in the aortic sinus and decreased serum CRP, MCP-1, and ox-LDL levels. These findings suggest that sublingual immunization with rGroEL is associated with the increase of IFN gamma(+) or IL-10(+) Foxp3(+) cells in SMG and a systemic humoral response, which could be an effective strategy for the prevention of naturally occurring or P. gingivalis-accelerated atherosclerosis.