Lethal tuberculosis in interleukin-6-deficient mutant mice
Lethal tuberculosis in interleukin-6-deficient mutant mice
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DOI：
10.1128/iai.65.11.4843-4849.1997
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发表时间：
1997-11-01
影响因子：
3.1
通讯作者：
Kaufmann, SHE
中科院分区：
文献类型：
--
作者：
Ladel, CH;Blum, C;Kaufmann, SHE
结核病是一种慢性传染病，在全球范围内造成重大健康问题。获得性抵抗力由T淋巴细胞介导，并由活化的巨噬细胞执行。体外研究强调了巨噬细胞活化对抑制分枝杆菌生长的重要性。在体内，宿主的保护性反应集中在含有结核分枝杆菌的肉芽肿病变上。辅助性T细胞1（Th1）型细胞免疫反应被认为对控制结核病至关重要。我们利用白细胞介素 - 6（IL - 6）缺陷型小鼠在此证明了这种多能细胞因子在抵抗结核分枝杆菌而非牛分枝杆菌卡介苗（BCG）方面的关键作用。用结核分枝杆菌感染时，在仍能被有IL - 6功能的小鼠所控制的接种量下，对IL - 6缺陷型小鼠是致命的。与对照水平相比，结核分枝杆菌感染的IL - 6（-/-）小鼠突变体的脾细胞产生更高水平的白细胞介素 - 4（IL - 4）和更低水平的γ干扰素。对结核分枝杆菌感染小鼠脾细胞的流式细胞术分析显示，IL - 6（-/-）小鼠的T细胞比例变化比对照小鼠更为显著。我们认为IL - 6通过其促炎活性以及对细胞因子分泌的影响有助于宿主的抵抗力。
Tuberculosis is a chronic infectious disease which causes major health problems globally. Acquired resistance is mediated by T lymphocytes and executed by activated macrophages. In vitro studies have emphasized the importance of macrophage activation for mycobacterial growth inhibition. In vivo, the protective host response is focused on granulomatous lesions in which Mycobacterium tuberculosis is contained. A cellular immune response of the T helper 1 (Th1) type is considered central for control of tuberculosis. Using interleukin-6 (IL-6)-deficient mice, we here demonstrate a crucial role of this pluripotent cytokine in protection against M. tuberculosis but not against Mycobacterium bovis EGG. Infection with M. tuberculosis was lethal for the IL-6-deficient mice at inocula that were still controlled by IL-6-competent mice. Spleen cells from M. tuberculosis-infected IL-6(-/-) mouse mutants produced elevated levels of IL-4 and reduced levels of gamma interferon compared to the control levels. Cytofluorometric analyses of spleen cells from M. tuberculosis-infected mice revealed more-profound alterations in T-cell ratios in IL-6(-/-) mice than in control mice. We assume that IL-6 contributes to host resistance by its proinflammatory activity and by its influence on cytokine secretion.