Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling.
Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling.
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DOI：
10.1126/sciimmunol.abf1198
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发表时间：
2021-09-10
影响因子：
24.8
通讯作者：
Kolls JK
中科院分区：
文献类型：
--
作者：
Iwanaga N;Chen K;Yang H;Lu S;Hoffmann JP;Wanek A;McCombs JE;Song K;Rangel-Moreno J;Norton EB;Kolls JK
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。本研究以克雷伯氏菌外膜蛋白（Omp）X为抗原，制备了一种疫苗. pneumoniae和LTA 1佐剂，通过肺内途径给药。该疫苗诱导的Th 1和Th 17细胞与热灭活K.肺炎。需要抗体应答来防止细菌传播，但需要肺特异性免疫。相反，肺免疫需要成纤维细胞中的CD 4 + T细胞、STAT 3表达和IL-17 R信号传导。在过继转移模型中，观察到来自OmpX+ LTA 1免疫小鼠的肺特异性CD 4 + T细胞归巢至肺，并且可以介导针对感染的保护。与Th 1细胞相比，疫苗诱导的Th 17细胞表现出可塑性降低，并且对免疫抑制剂FK 506具有抗性，并且Th 17细胞在移植免疫抑制条件下赋予保护作用。这些数据证明了一种新的疫苗策略，该策略可以刺激肺TRM细胞并促进对K.肺炎。亚单位粘膜疫苗通过肺成纤维细胞中的IL-17 R信号传导赋予针对异源肺炎克雷伯氏菌菌株的保护作用。
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 K. pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both Th1 and Th17 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 Th17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with Th1 cells, and Th17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a novel vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae. A subunit mucosal vaccine conferred protection against heterologous Klebsiella pneumoniae strains, via IL-17R signaling in lung fibroblasts.
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DOI：
10.1073/pnas.1121383109
发表时间：
2012-03-06
影响因子：
11.1
作者：
Malley, Richard;Anderson, Porter W.
通讯作者：
Anderson, Porter W.
影响因子：
3.1
作者：
Maciel, Milton, Jr.;Bauer, David;Norton, Elizabeth B.
通讯作者：
Norton, Elizabeth B.
影响因子：
8
作者：
Iwanaga, Naoki;Sandquist, Ivy;Kolls, Jay K.
通讯作者：
Kolls, Jay K.
影响因子：
3
作者：
Exner M;Bhattacharya S;Christiansen B;Gebel J;Goroncy-Bermes P;Hartemann P;Heeg P;Ilschner C;Kramer A;Larson E;Merkens W;Mielke M;Oltmanns P;Ross B;Rotter M;Schmithausen RM;Sonntag HG;Trautmann M
通讯作者：
Trautmann M
影响因子：
7.3
作者：
Hutloff A
通讯作者：
Hutloff A