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.

Increased male susceptibility to Mycobacterium tuberculosis infection is associated with smaller B cell follicles in the lungs

“…Identifying common denominators of male susceptibility for different members of the Mtbc may facilitate the development of novel therapeutic or preventive approaches that restore clinically-relevant immune responses in a sex-specific manner. Of note, lymphoid follicles not only form during Mtb infection but also upon mucosal vaccination, which induces superior protection against TB in animal models [36][37][38][39] . These vaccination studies suggest that the interplay between B and T cells is critical for the proper development of protective immune responses to TB and corroborate previous studies which demonstrated the importance of B cells for control of TB [40][41][42] .…”

Lymphoid Tissue–Resident Alcaligenes Establish an Intracellular Symbiotic Environment by Creating a Unique Energy Shift in Dendritic Cells

“…Flow cytometry was performed as previously described (Nagatake et al, 2018). BMDCs were collected by using trypsin-EDTA solution (Nacalai Tesque) and suspended in PBS containing 2% (vol/vol) newborn calf serum (Equitech-Bio, Kerrville, TX, United States).…”

Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation

“…However, recent reports have shown that DC migration toward peripheral areas is crucial for fine-tuning immune responses. [2][3][4]56 Migrated DCs form clusters and drive peripheral T cell expansion and B cell-mediated immunity; thus, DC migration to the lymph nodes and inflamed peripheral areas is important for regulating acquired immunity. These reports lead us to hypothesize that the formerly identified canonical DCs are in fact BLT1 lo DCs and the latter noncanonical DCs are in fact BLT1 hi DCs.…”