The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis.
The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis.
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DOI：
10.1111/j.1600-065x.2008.00702.x
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发表时间：
2008-12
影响因子：
8.7
通讯作者：
Khader SA
中科院分区：
文献类型：
--
作者：
Cooper AM;Khader SA
结核病（TB）是一种强效免疫反应和慢性持续性病原体相互作用的结果。结核分枝杆菌（Mtb）能够诱导强烈的免疫反应，同时能够抵抗宿主清除细菌的能力，这为研究特定细胞因子途径在诱导、扩增和控制效应t细胞反应中的作用提供了一个很好的工具。本文综述了白细胞介素-12p40 （IL-12p40）、IL-12p70、IL-23和IL-27在Mtb免疫应答中的作用。我们发现IL-12(p40)2介导树突状细胞的激活，使其对稳态趋化因子产生反应。我们还发现IL-12p70是最佳干扰素-γ (IFN-γ) t细胞反应所必需的，这是控制结核分枝杆菌生长所必需的。如果IL-12不存在，IL-23可以诱导肺内IFN-γ反应，但其主要作用是支持肺内IL-17反应。无论是IL-23还是IL-17都不需要用于肺中Mtb的早期控制。然而，IL-23和IL-17可以在疫苗诱导的保护中发挥作用。最后，IL-27限制了肺部的保护性免疫，但它也是长期生存所必需的。因此，这些细胞因子在结核病免疫反应中起着关键作用。
Tuberculosis (TB) results from an interaction between a potent immune response and a chronically persistent pathogen. The ability of Mycobacterium tuberculosis (Mtb) to induce a strong immune response while being able to resist the ability of the host to clear bacteria provides an excellent tool with which to investigate the role of specific cytokine pathways on the induction, expansion, and control of the effector T-cell response. In this review, the role of interleukin-12p40 (IL-12p40), IL-12p70, IL-23, and IL-27 in the immune response to Mtb are described. We show that IL-12(p40)2 acts to mediate the activation of dendritic cells to become responsive to homeostatic chemokines. We also show that IL-12p70 is required for the optimal interferon-γ (IFN-γ) T-cell response, which is required for control of Mtb growth. IL-23 can induce IFN-γ responses in the lung if IL-12 is not present, but its major role is in supporting the IL-17 response within the lung. Neither IL-23 nor IL-17 is required for early control of Mtb in the lung. IL-23 and IL-17, however, can be instrumental in vaccine-induced protection. Finally, IL-27 limits protective immunity in the lung, but it is also required for long-term survival. These cytokines are therefore key players in the immune response to TB.