Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis.
Dynamic roles of type I and type II IFNs in early infection with Mycobacterium tuberculosis.
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DOI：
10.4049/jimmunol.1200255
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发表时间：
2012-06-15
期刊：
影响因子：
--
通讯作者：
Ernst JD
中科院分区：
文献类型：
--
作者：
Desvignes L;Wolf AJ;Ernst JD
尽管II型干扰素（IFN）或IFN-γ对结核分枝杆菌的保护作用已经确立，但I型干扰素的作用仍不清楚。一个潜在的混淆因素是两种信号通路之间的功能重叠。我们使用携带I型IFN受体、II型IFN受体或两者均为零突变的小鼠，并将其与野生型小鼠在气溶胶感染结核分枝杆菌后的免疫反应进行比较。我们发现，在对IFN-γ没有反应的情况下，I型IFN对结核病起着非冗余的保护作用。对两种干扰素均无反应的小鼠在相似细菌负荷下的肺组织病理更严重，且死亡时间明显早于干扰素-γ信号受损的小鼠。我们排除了I型IFN在T细胞募集中的作用，这是IFN-γ依赖性的，而两种类型的IFN都是最佳NK细胞募集到肺部所必需的。I型干扰素对肺髓细胞群的组成具有时间依赖性影响，特别是在适应性免疫开始后，通过限制结核分枝杆菌感染的募集巨噬细胞的丰度。我们证实，对IFN-γ的反应对控制细胞内分枝杆菌生长至关重要，而I型IFN没有任何额外的作用。总之，我们的研究结果暗示了一个模型，在这个模型中，I型IFN限制了结核分枝杆菌可以感染肺部的靶细胞数量，而IFN-γ增强了它们限制细菌生长的能力。
Whereas the protective role of type II interferon (IFN), or IFN-γ, against Mycobacterium tuberculosis has been established, the effects of type I IFNs are still unclear. One potential confounding factor is the overlap of function between the two signaling pathways. We used mice carrying null mutations in type I IFN receptor, type II IFN receptor or both and compared their immune responses to those of wild type mice following aerosol infection with M. tuberculosis. We discovered that, in the absence of response to IFN-γ, type I IFNs play a non-redundant protective role against tuberculosis. Mice unable to respond to both types of IFNs had more severe lung histopathology for similar bacterial loads and died significantly earlier than mice with impaired IFN-γ signaling alone. We excluded a role for type I IFN in T cell recruitment, which was IFN-γ-dependent, while both types of IFNs were required for optimal NK cell recruitment to the lungs. Type I IFN had a time-dependent influence on the composition of lung myeloid cell populations, in particular by limiting the abundance of M. tuberculosis-infected recruited macrophages after the onset of adaptive immunity. We confirmed that response to IFN-γ was essential to control intracellular mycobacterial growth, without any additional effect of type I IFN. Together, our results imply a model in which type I IFN limit the number of target cells that M. tuberculosis can infect in the lungs while IFN-γ enhances their ability to restrict bacterial growth.
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