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

在小鼠中,Ag85B-rHPIV2疫苗诱导的抗结核黏膜免疫反应与诱导性支气管相关淋巴组织器官发生存在免疫学关联

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作者:Takahiro Nagatake ,Hidehiko Suzuki ,So-Ichiro Hirata ,Naomi Matsumoto ,Yasuko Wada ,Sakiko Morimoto ,Ayaka Nasu ,Michiko Shimojou ,Mitsuo Kawano ,Kentaro Ogami ,Yusuke Tsujimura ,Etsushi Kuroda ,Norifumi Iijima ,Koji Hosomi ,Ken J Ishii ,Tetsuya Nosaka ,Yasuhiro Yasutomi ,Jun Kunisawa

Abstract

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.

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