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

摘要: Brucellosis remains the most common zoonotic disease globally. Currently no vaccines for humans exist, and conventional brucellosis livestock fail to confer complete protection; hence, an improved vaccine is needed. Although Brucella infections primarily occur following a mucosal exposure, are administered parenterally. Few studies have considered vaccinations, or even targeting of tissue-resident memory T (TRM) cells. TRM cells protect against viral infections, but less known their role in bacterial brucellosis. Oral prime, nasal boost with newly developed abortus double mutant (znBAZ) confers nearly protection pulmonary challenge wild-type (wt) B. 2308, its protective efficacy >2800-fold better than RB51 vaccine. Vaccination znBAZ potently stimulated CD8+ cells, whereas vaccination induced mostly CD4+ Subsequent analysis revealed these CD44+ CD69+ be either CD103+ CD103- sequestered lung parenchyma as CXCR3lo airways CXCR3hi. Both subsets contained single-positive IFN-γ TNF-α, well as, polyfunctional IL-17-producing were also by vaccination, vivo IL-17 neutralization had impact upon protection. In depletion znBAZ-vaccinated mice. contrast, cell reduced RB51's spleens lungs two- three-logs, respectively. anti-CD8 mAb-treated mice showed significantly efficacy, this treatment failed completely deplete leaving ratios intact. Only CD8-/- fully sensitive virulent wt 2308 since could not induced. Collectively, data demonstrate key generation protecting abortus.