Journal
INTERNATIONAL IMMUNOLOGY
Volume 30, Issue 10, Pages 471-481Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxy046
Keywords
iBALT; mucosa-associated lymphoid tissue; mucosal immunity; tertiary lymphoid organ; nasal vaccine
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Funding
- Japan Agency for Medical Research and Development (AMED) [JP17fk0108107h0002, JP17ak0101068h0001, JP17fm0208011h0001]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Japan Society for the Promotion of Science (JSPS) (MEXT/JSPS KAKENHI) [JP15K19142, JP17K08301, JP24591145, JP16H05256, JP18J00556, JP18K17997, JP18H02857, JP18H02674]
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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 gamma-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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