Abstract:
Bordetella spp. are respiratory pathogens equipped with immune evasion mechanisms. We previously characterized a Bordetella bronchiseptica mutant (RB50ΔbtrS) that fails to suppress host responses, leading to rapid clearance and long-lasting immunity against reinfection. This work revealed eosinophils as an exclusive requirement for RB50ΔbtrS clearance. We also show that RB50ΔbtrS promotes eosinophil-mediated B/T cell recruitment and inducible bronchus-associated lymphoid tissue (iBALT) formation, with eosinophils being present throughout iBALT for Th17 and immunoglobulin A (IgA) responses. Finally, we provide evidence that XCL1 is critical for iBALT formation but not maintenance, proposing a novel role for eosinophils as facilitators of adaptive immunity against B. bronchiseptica. RB50ΔbtrS being incapable of suppressing eosinophil effector functions illuminates active, bacterial targeting of eosinophils to achieve successful persistence and reinfection. Overall, our discoveries contribute to understanding cellular mechanisms for use in future vaccines and therapies against Bordetella spp. and extension to other mucosal pathogens.
摘要:
博德特氏菌属。是具有免疫逃避机制的呼吸道病原体。我们先前表征了支气管败血波氏杆菌突变体(RB50ΔbtrS)无法抑制宿主反应,导致快速清除和持久的免疫抵抗再感染。这项工作揭示了嗜酸性粒细胞是RB50ΔbtrS清除的唯一要求。我们还显示RB50ΔbtrS促进嗜酸性粒细胞介导的B/T细胞募集和可诱导的支气管相关淋巴组织(iBALT)形成,嗜酸性粒细胞存在于整个iBALT中,用于Th17和免疫球蛋白A(IgA)反应。最后,我们提供的证据表明,XCL1对iBALT形成至关重要,但不是维持,提出嗜酸性粒细胞作为针对支气管败血杆菌的适应性免疫的促进剂的新作用。RB50ΔbtrS不能抑制嗜酸性粒细胞效应子功能,嗜酸性粒细胞的细菌靶向实现成功的持续和再感染。总的来说,我们的发现有助于理解细胞机制用于未来针对博德特氏菌属的疫苗和疗法.并延伸到其他粘膜病原体。