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

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.

• Authors: 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
• Journal: International immunology (Int Immunol) Vol. 30 Issue 10 Pg. 471-481 (09 25 2018) ISSN: 1460-2377 [Electronic] England
• PMID: 30011025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Tuberculosis Vaccines
• Acyltransferases
• antigen 85A, Mycobacterium tuberculosis

Topics

• Acyltransferases (immunology)
• Animals
• Antigens, Bacterial (immunology)
• Lymphoid Tissue (immunology)
• Mice
• Mice, Inbred C57BL
• Mycobacterium tuberculosis (immunology)
• Organogenesis
• Parainfluenza Virus 2, Human (immunology)
• Tuberculosis Vaccines (immunology)