Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice
Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice
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DOI：
10.1111/j.1365-2249.2006.03092.x
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发表时间：
2006-06-01
影响因子：
4.6
通讯作者：
Mitsuyama, M.
中科院分区：
文献类型：
--
作者：
Yamamoto, K.;Kawamura, I.;Mitsuyama, M.
来源于单核细胞增生李斯特菌的李斯特菌溶血素O（LLO）具有高度诱导白细胞介素（IL）-12、IL-18和干扰素（IFN）-γ的能力，并促进Th 1细胞的产生。我们最近已经表明，重组LLO（rLLO）抑制卵清蛋白（OVA）特异性的Th 2免疫应答的产生，通过倾斜的抗原特异性T细胞成熟为Th 1细胞。在本研究中，我们研究了rLLO对OVA致敏的BALB/c小鼠的Th 2依赖性变应性鼻炎的效应相的影响。在腹腔内致敏和OVA鼻内激发的小鼠中，观察到高频率的鼻过敏症状，如打喷嚏和抓鼻。血清中检测到高滴度的抗OVA IgE抗体，大量嗜酸性粒细胞迁移到鼻组织中。然而，rLLO治疗鼻内攻击期间抑制过敏症状，抗OVA IgE抗体的产生和嗜酸性粒细胞浸润。虽然rLLO不影响脾CD 4（+）T细胞产生抗原特异性细胞因子，但rLLO显著抑制鼻单核细胞产生OVA特异性IL-4和IL-5。rLLO可抑制鼻粘膜CD 4 + T细胞的募集，并抑制脾CD 4 + T细胞CCR 4的转录和细胞表面表达。此外，rLLO能够抑制过敏性抗体（IgE和IgG（1））和肥大细胞介导的被动皮肤过敏反应。总之，这些数据表明，rLLO通过抑制Th 2细胞向鼻粘膜的募集和I型过敏反应来抑制过敏性鼻炎的效应相。
Listeriolysin O (LLO) derived from Listeria monocytogenes is highly capable of inducing interleukin (IL)-12, IL-18 and interferon (IFN)-gamma, and facilitates the generation of Th1 cells. We have recently shown that recombinant LLO (rLLO) inhibits generation of ovalbumin (OVA)-specific Th2 immune response by skewing maturation of antigen-specific T cells into Th1 cells. In the present study, we investigated the effect of rLLO on the effector phase of Th2-dependent allergic rhinitis in BALB/c mice sensitized with OVA. In mice sensitized intraperitoneally and challenged intranasally with OVA, nasal allergic symptoms such as sneezing and nose-scratching were observed at a high frequency. A high titre of anti-OVA IgE antibody was detected in sera and a large number of eosinophils migrated into the nasal tissue. However, rLLO treatment during the intranasal challenge inhibited the allergic symptoms, production of anti-OVA IgE antibody and eosinophil infiltration. Though rLLO did not affect antigen-specific cytokine production from splenic CD4(+) T cells, rLLO significantly suppressed OVA-specific IL-4 and IL-5 production from nasal mononuclear cells. We further found that rLLO inhibited the recruitment of CD4(+) T cells in nasal mucosa, and diminished the transcription and cell surface expression of CCR4 on splenic CD4(+) T cells. Moreover, rLLO was able to inhibit the passive cutaneous anaphylaxis reaction mediated by anaphylactic antibodies (IgE and IgG(1)) and mast cells. Taken together, these data showed that rLLO suppresses the effector phase of allergic rhinitis by inhibition of Th2 cell recruitment to nasal mucosa and type I allergic reaction.