Intranasal immunization with Mycobacterium tuberculosis Rv3615c induces sustained adaptive CD4(+) T-cell and antibody responses in the respiratory tract.
Intranasal immunization with Mycobacterium tuberculosis Rv3615c induces sustained adaptive CD4(+) T-cell and antibody responses in the respiratory tract.
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结核分枝杆菌 Rv3615c 鼻内免疫诱导呼吸道持续适应性 CD4 T 细胞和抗体反应
DOI：
10.1111/jcmm.13965
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发表时间：
2019-01
影响因子：
5.3
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Li J;Zhao J;Shen J;Wu C;Liu J
对病原体的持续适应性免疫提供有效的抗感染保护，位于感染部位的效应细胞确保对挑战的快速反应。这两者对于疫苗开发的成功至关重要。为了探索针对结核分枝杆菌（M.tb）感染的新疫苗接种方法，我们已经证明，Rv 3615 c（被鉴定为M.tb的ESX‐1底物蛋白C，但在BCG中不表达）诱导了结核性胸膜炎患者CD 4 + T细胞的显性Th 1型应答，这表明了疫苗开发的潜在候选者。但是用Rv 3615 c皮下免疫诱导了适度的全身性T细胞应答，并且在感染部位显示出针对毒性结核分枝杆菌攻击的次优保护。在这里，我们使用小鼠模型来证明用Rv 3615 c鼻内免疫诱导肺实质和气道中适应性CD 4 + T-和B-细胞应答的持续能力。Rv 3615 c含有小鼠CD 4 + T细胞的优势表位Rv 3615 c41 - 50，并具有效应记忆表型和多Th 1型细胞因子共表达的激发性CD 4 + T细胞应答。由于驻留在粘膜组织中的T细胞在早期阶段控制感染是有效的，我们的数据显示用Rv 3615 c鼻内免疫促进对结核分枝杆菌的持续区域免疫，并表明控制结核分枝杆菌感染的效力。我们的研究保证了Rv 3615 c作为开发针对结核分枝杆菌感染的有效疫苗的候选物的进一步研究。
Sustained adaptive immunity to pathogens provides effective protection against infections, and effector cells located at the site of infection ensure rapid response to the challenge. Both are essential for the success of vaccine development. To explore new vaccination approach against Mycobacterium tuberculosis (M.tb) infection, we have shown that Rv3615c, identified as ESX‐1 substrate protein C of M.tb but not expressed in BCG, induced a dominant Th1‐type response of CD4+ T cells from patients with tuberculosis pleurisy, which suggests a potential candidate for vaccine development. But subcutaneous immunization with Rv3615c induced modest T‐cell responses systemically, and showed suboptimal protection against virulent M.tb challenge at the site of infection. Here, we use a mouse model to demonstrate that intranasal immunization with Rv3615c induces sustained capability of adaptive CD4+ T‐ and B‐cell responses in lung parenchyma and airway. Rv3615c contains a dominant epitope of mouse CD4+ T cells, Rv3615c41‐50, and elicits CD4+ T‐cell response with an effector–memory phenotype and multi‐Th1‐type cytokine coexpressions. Since T cells resident at mucosal tissue are potent at control of infection at early stage, our data show that intranasal immunization with Rv3615c promotes a sustained regional immunity to M.tb, and suggests a potency in control of M.tb infection. Our study warranties a further investigation of Rv3615c as a candidate for development of effective vaccination against M.tb infection.
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DOI：
10.4049/jimmunol.1101122
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
通讯作者：
Hanekom WA
影响因子：
64.5
作者：
Fan X;Rudensky AY
通讯作者：
Rudensky AY
影响因子：
5.5
作者：
Boggiano C;Eichelberg K;Ramachandra L;Shea J;Ramakrishnan L;Behar S;Ernst JD;Porcelli SA;Maeurer M;Kornfeld H
通讯作者：
Kornfeld H
影响因子：
3.2
作者：
Fisher, MA;Plikaytis, BB;Shinnick, TM
通讯作者：
Shinnick, TM
影响因子：
6.4
作者：
Coler, Rhea N.;Bertholet, Sylvie;Reed, Steven G.
通讯作者：
Reed, Steven G.