Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice.

Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice.
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DOI:
10.1093/intimm/dxy046
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发表时间:
2018-09-25
影响因子:
4.4
通讯作者:
Kunisawa J
Kunisawa J
中科院分区:
医学3区
文献类型:
--
作者:
Nagatake T;Suzuki H;Hirata SI;Matsumoto N;Wada Y;Morimoto S;Nasu A;Shimojou M;Kawano M;Ogami K;Tsujimura Y;Kuroda E;Iijima N;Hosomi K;Ishii KJ;Nosaka T;Yasutomi Y;Kunisawa J

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我们以前报道,表达Ag 85 B的人副流感病毒2型(Ag 85 B-rHPIV 2)是有效的鼻疫苗对小鼠结核病,但是,它诱导免疫应答的机制仍有待研究。在本研究中,我们发现,诱导型支气管相关淋巴组织(iBALT)的器官形成在鼻内注射Ag 85 B-rHPIV 2的小鼠肺中抗原特异性T细胞和伊加抗体应答的诱导中发挥作用。我们发现Ag 85 B的表达与iBALT的发生有关,表明HPIV 2作为iBALT的诱导载体。当Ag 85 B-rHPIV 2免疫小鼠中的iBALT器官发生被破坏时,无论是通过中和光敏素途径还是耗尽CD 11b+细胞,肺中的Ag 85 B特异性免疫应答(即产生IFN γ的T细胞和伊加抗体)都会减弱。此外,我们发现用Ag 85 B-rHPIV 2免疫诱导中性粒细胞和嗜酸性粒细胞浸润在免疫后的时间在肺中。因此,我们的研究结果表明,iBALT器官形成有助于抗原特异性免疫应答的诱导Ag 85 B-rHPIV 2和Ag 85 B-rHPIV 2激发其免疫应答,而不诱导持久的炎症。一种基于副流感的鼻疫苗诱导肺中BALT的形成
We previously reported that Ag85B-expressing human parainfluenza type 2 virus (Ag85B-rHPIV2) was effective as a nasal vaccine against tuberculosis in mice; however, the mechanism by which it induces an immune response remains to be investigated. In the present study, we found that organogenesis of inducible bronchus-associated lymphoid tissue (iBALT) played a role in the induction of antigen-specific T cells and IgA antibody responses in the lung of mice intra-nasally administered Ag85B-rHPIV2. We found that expression of Ag85B was dispensable for the development of iBALT, suggesting that HPIV2 acted as an iBALT-inducing vector. When iBALT organogenesis was disrupted in Ag85B-rHPIV2-immunized mice, either by neutralization of the lymphotoxin pathway or depletion of CD11b+ cells, Ag85B-specific immune responses (i.e. IFN γ-producing T cells and IgA antibody) were diminished in the lung. Furthermore, we found that immunization with Ag85B-rHPIV2 induced neutrophil and eosinophil infiltration temporally after the immunization in the lung. Thus, our results show that iBALT organogenesis contributes to the induction of antigen-specific immune responses by Ag85B-rHPIV2 and that Ag85B-rHPIV2 provokes its immune responses without inducing long-lasting inflammation. A parainfluenza-based nasal vaccine induces formation of BALT in the lung
树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
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