English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Brucellosis remains the most common zoonotic disease globally. Currently no vaccines for humans exist, and conventional brucellosis vaccines for livestock fail to confer complete protection; hence, an improved vaccine is needed. Although  Brucella  infections primarily occur following a mucosal exposure, vaccines are administered parenterally. Few studies have considered mucosal vaccinations, or even targeting of tissue-resident memory T (T RM ) cells. T RM  cells protect against viral infections, but less is known of their role in bacterial infections, and even less for brucellosis. Oral prime, nasal boost with a newly developed  Brucella abortus  double mutant (znBAZ) confers nearly complete protection against pulmonary challenge with wild-type (wt)  B .  abortus  2308, and its protective efficacy is >2800-fold better than the RB51 vaccine. Vaccination with znBAZ potently stimulated CD8 +  T cells, whereas mucosal vaccination with RB51 induced mostly CD4 +  T cells. Subsequent analysis revealed these pulmonary CD44 +  CD69 +  CD8 +  T cells to be either CD103 +  or CD103 -  T RM  cells, and these sequestered to the lung parenchyma as CXCR3 lo  and to the airways as CXCR3 hi . Both CD8 +  T RM  subsets contained single-positive IFN-γ and TNF-α, as well as, polyfunctional cells. IL-17-producing CD8 +  T RM  cells were also induced by znBAZ vaccination, but  in vivo  IL-17 neutralization had no impact upon protection.  In vivo  depletion of CD4 +  T cells had no impact upon protection in znBAZ-vaccinated mice. In contrast, CD4 +  T cell depletion reduced RB51’s protective efficacy in spleens and lungs by two- and three-logs, respectively. Although anti-CD8 mAb-treated znBAZ-vaccinated mice showed a significantly reduced pulmonary efficacy, this treatment failed to completely deplete the lung CD8 +  T cells, leaving the CD103 +  and CD103 -  CD8 +  T RM  cell ratios intact. Only znBAZ-vaccinated CD8 -/-  mice were fully sensitive to pulmonary challenge with virulent wt  B .  abortus  2308 since CD8 +  T RM  cells could not be induced. Collectively, these data demonstrate the key role of mucosal vaccination for the generation of CD8 +  T RM  cells in protecting against pulmonary challenge with virulent  B .  abortus .

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection