Tissue-resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from Klebsiella pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both T_H1 and T_H17 cells that shared transcriptional features with cells elicited by heat-killed K. pneumoniae. Antibody responses were required to prevent bacterial dissemination but dispensable for lung-specific immunity. In contrast, lung immunity required CD4⁺ T cells, STAT3 expression, and IL-17R signaling in fibroblasts. Lung-specific CD4⁺ T cells from OmpX+LTA1–immunized mice were observed homing to the lung and could mediate protection against infection in an adoptive transfer model. Vaccine-elicited T_H17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with T_H1 cells, and T_H17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a promising vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae.

中文翻译：

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疫苗驱动的肺 TRM 细胞通过成纤维细胞 IL-17R 信号传导提供针对克雷伯氏菌的免疫力

组织驻留记忆 (TRM) 细胞被认为在肺粘膜对病原体的免疫中发挥作用，但通过粘膜疫苗引发 TRM 的策略尚未完全实现。在这里，我们配制了一种由肺炎克雷伯菌的外膜蛋白 (Omp) X和 LTA1 佐剂组成的疫苗，该疫苗通过肺内途径给药。这种疫苗诱导出的 T _H 1 和 T _H 17 细胞与热灭活的肺炎克雷伯菌诱导的细胞具有相同的转录特征。需要抗体反应来防止细菌传播，但对于肺特异性免疫却是可有可无的。相比之下，肺免疫需要 CD4 ⁺成纤维细胞中的 T 细胞、STAT3 表达和 IL-17R 信号传导。观察到来自 OmpX+LTA1 免疫小鼠的肺特异性 CD4 ^{+ T 细胞归巢至肺，并且可以在过继转移模型中介导对感染的保护。}_{与 T H} 1 细胞相比，疫苗诱导的 T _H 17 细胞可塑性降低，并且对免疫抑制剂 FK506 具有抗性，并且 T _H 17 细胞在移植免疫抑制条件下具有保护作用。这些数据证明了一种有希望的疫苗策略，它可以诱导肺 TRM 细胞并促进对肺炎克雷伯菌的非血清型依赖性免疫。